| General information | | DisProt: | DP00716_C001 | | Name: | Lamin A/C | | Synonym(s): | LMNA_HUMAN
cleavage product 1 of Prelamin-A/C
70 kDa lamin
Renal carcinoma antigen NY-REN-32
Lamin C is Isoform P02545-2
| | First appeared in release: | Release 5.8 (07/21/2011) | | UniProt: | P02545 | | UniGene: | | | SwissProt: | LMNA_HUMAN | | TrEMBL: | | | NCBI (GI): | | | Source organism: | Homo sapiens (Human) | | Sequence length: | 646 | | Percent disordered: | 14% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
| | | | | |
METPSQRRAT RSGAQASSTP LSPTRITRLQ EKEDLQELND RLAVYIDRVR SLETENAGLR - 60
LRITESEEVV SREVSGIKAA YEAELGDARK TLDSVAKERA RLQLELSKVR EEFKELKARN - 120
TKKEGDLIAA QARLKDLEAL LNSKEAALST ALSEKRTLEG ELHDLRGQVA KLEAALGEAK - 180
KQLQDEMLRR VDAENRLQTM KEELDFQKNI YSEELRETKR RHETRLVEID NGKQREFESR - 240
LADALQELRA QHEDQVEQYK KELEKTYSAK LDNARQSAER NSNLVGAAHE ELQQSRIRID - 300
SLSAQLSQLQ KQLAAKEAKL RDLEDSLARE RDTSRRLLAE KEREMAEMRA RMQQQLDEYQ - 360
ELLDIKLALD MEIHAYRKLL EGEEERLRLS PSPTSQRSRG RASSHSSQTQ GGGSVTKKRK - 420
LESTESRSSF SQHARTSGRV AVEEVDEEGK FVRLRNKSNE DQSMGNWQIK RQNGDDPLLT - 480
YRFPPKFTLK AGQVVTIWAA GAGATHSPPT DLVWKAQNTW GCGNSLRTAL INSTGEEVAM - 540
RKLVRSVTVV EDDEDEDGDD LLHHHHGSHC SSSGDPAEYN LRSRTVLCGT CGQPADKASA - 600
SGSGAQVGGP ISSGSSASSV TVTRSYRSVG GSGGGSFGDN LVTRSY
|
| Functional narrative |
Function: Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Play an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.
Function: Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.
SUBUNIT: Homodimer of lamin A and lamin C. Interacts with lamin- associated polypeptides IA, IB and TMPO-alpha, RB1 and with emerin. Interacts with SREBF1, SREBF2, SUN2 and TMEM43 (By similarity). Proteolytically processed isoform A interacts with NARF. Interacts with SUN1. Prelamin-A/C interacts with EMD. P18054:ALOX12; NbExp=3; IntAct=EBI-351935, EBI-1633210;
Subcellular Location: Nucleus. Nucleus envelope. Note=Farnesylation of prelamin-A/C facilitates nuclear envelope targeting and subsequent cleaveage by ZMPSTE24/FACE1 to remove the farnesyl group produces mature lamin-A/C, which can then be inserted into the nuclear lamina. EMD is required for proper localization of non-farnesylated prelamin-A/C. Event=Alternative splicing; Named isoforms=3; Name=A; Synonyms=Lamin A; IsoId=P02545-1; Sequence=Displayed; Name=C; Synonyms=Lamin C; IsoId=P02545-2; Sequence=VSP_002469, VSP_002470; Name=ADelta10; Synonyms=Lamin ADelta10; IsoId=P02545-3; Sequence=VSP_002468;
TISSUE SPECIFICITY: In the arteries, prelamin-A/C accumulation is not observed in young healthy vessels but is prevalent in medial vascular smooth muscle celle (VSMCs) from aged individuals and in atherosclerotic lesions, where it often colocalizes with senescent and degenerate VSMCs. Prelamin-A/C expression increases with age and disease. In normal aging, the accumulation of prelamin-A/C is caused in part by the down-regulation of ZMPSTE24/FACE1 in response to oxidative stress.
PTM: Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations.
PTM: Proteolytic cleavage of the C-terminal of 18 residues of prelamin-A/C results in the production of lamin-A/C. The prelamin- A/C maturation pathway includes farnesylation of CAAX motif, ZMPSTE24/FACE1 mediated cleavage of the last three amino acids, methylation of the C-terminal cysteine and endoproteolytic removal of the last 15 C-terminal amino acids. Proteolytic cleavage requires prior farnesylation and methylation, and absence of these blocks cleavage.
PTM: Sumoylation is necessary for the localization to the nuclear envelope.
PTM: Farnesylation of prelamin-A/C facilitates nuclear envelope targeting.
DISEASE: Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2 (EDMD2), cardiomyopathy dilated type 1A (CMD1A), familial partial lipodystrophy type 2 (FPLD2), limb-girdle muscular dystrophy type 1B (LGMD1B), Charcot-Marie-Tooth disease type 2B1 (CMT2B1), Hutchinson-Gilford progeria syndrome (HGPS), cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH), mandibuloacral dysplasia with type A lipodystrophy (MADA), lethal tight skin contracture syndrome (LTSCS) also known as restrictive dermopathy (RD), heart-hand syndrome Slovenian type (HHS-Slovenian), muscular dystrophy congenital LMNA-related (CMD-LMNA),
MISCELLANEOUS: There are three types of lamins in human cells: A, B, and C.
MISCELLANEOUS: The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.
SIMILARITY: Belongs to the intermediate filament family. Sequence=CAA27173.1; Type=Frameshift; Positions=582;
WEB RESOURCE: Name=Human Intermediate Filament Mutation Database; URL='http://www.interfil.org';
WEB RESOURCE: Name=GeneReviews; URL='http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LMNA'.
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|
| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
|
| Region 1 | | Type: | Disordered | | Name: | N-terminal of C-terminal domain | | Location: | 411 - 430 | | Length: | 20 | | Region sequence: |
GGGSVTKKRKLESTESRSSF | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Flexible linkers/spacers
Nuclear localization
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; EDTA 1 mM; Lamin A/C (0.1-1.0mM); Phosphate (buffer) 20 mM; DTT 2 mM; NaN3 0.1 mM; 90% H2O, 10% D2O)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| Region 2 | | Type: | Ordered | | Name: | β-strand 1 | | Location: | 431 - 436 | | Length: | 6 | | Region sequence: |
SQHART | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
Protein-DNA binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| Region 3 | | Type: | Disordered | | Name: | Loop β1β2 | | Location: | 437 - 440 | | Length: | 4 | | Region sequence: |
SGRV | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-protein binding
Protein-DNA binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| Region 4 | | Type: | Ordered | | Name: | β-strand 2 (A) | | Location: | 441 - 446 | | Length: | 6 | | Region sequence: |
AVEEVD | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; Lamin A/C (0.1-1.0mM); Phosphate (buffer) 20 mM; DTT 2 mM; EDTA 1 mM; NaN3 0.1 mM; 90% H2O, 10% D2O)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Krimm et al (2002) describe two classic β-bulges, one involving E443, E444 and R453, the other involving I531, V538 and A539.
|
| Region 5 | | Type: | Disordered | | Name: | Loop β2β3 (AB) | | Location: | 447 - 450 | | Length: | 4 | | Region sequence: |
EEGK | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; Lamin A/C (0.1-1.0mM); Phosphate (buffer) 20 mM; DTT 2 mM; EDTA 1 mM; NaN3 0.1 mM; 90% H2O, 10% D2O)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| Region 6 | | Type: | Ordered | | Name: | β-strand 3 (B) | | Location: | 451 - 455 | | Length: | 5 | | Region sequence: |
FVRLR | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
- Circular dichroism (CD) spectroscopy, far-UV (283 K; Lamin A/C 1 mL; Temperature range 283-363K)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Experiments by Krimm et al (2002) on a representative laminopathy-related hotspot mutation, R453W, indicate this mutation causes destabilization of the C-domain structure.
Krimm et al (2002) describe two classic β-bulges, one involving E443, E444 and R453, the other involving I531, V538 and A539.
|
| Region 7 | | Type: | Disordered | | Name: | Loop β3β4 (BC) | | Location: | 456 - 467 | | Length: | 12 | | Region sequence: |
NKSNEDQSMGNW | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Loop β3β4 (BC) contains a β-strand at S458-S463.
|
| Region 8 | | Type: | Ordered | | Name: | β-strand 4 (C) | | Location: | 468 - 473 | | Length: | 6 | | Region sequence: |
QIKRQN | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the ordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| Region 9 | | Type: | Disordered | | Name: | Loop β4β5 (CC') | | Location: | 474 - 477 | | Length: | 4 | | Region sequence: |
GDDP | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| Region 10 | | Type: | Ordered | | Name: | β-strand 5 (C') | | Location: | 478 - 482 | | Length: | 5 | | Region sequence: |
LLTYR | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
- Circular dichroism (CD) spectroscopy, far-UV (283 K; Lamin A/C 1 mL; Temperature range 283-363K)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Experiments by Krimm et al (2002) on lipodystrophy-related hotspot mutations at R482 indicate a reduction of the positively charged character, resulting in perturbation of a key binding site.
|
| Region 11 | | Type: | Disordered | | Name: | Loop β5β6 (C'E) | | Location: | 483 - 493 | | Length: | 11 | | Region sequence: |
FPPKFTLKAGQ | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Loop β5β6 (C'E) contains a β-strand at F487-A491.
|
| Region 12 | | Type: | Ordered | | Name: | β-strand 6 (E) | | Location: | 494 - 499 | | Length: | 6 | | Region sequence: |
VVTIWA | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| Region 13 | | Type: | Disordered | | Name: | Loop β6β7 (EF) | | Location: | 500 - 510 | | Length: | 11 | | Region sequence: |
AGAGATHSPPT | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:At the end of Loop β6β7, Krimm et al (2002) describe a highly conserved Pro-Pro motif (a cis peptide bond between P508 and P509) that is "conserved in all lamins and in most of the invertebrate intermediate filaments."
Loop (EF) is comprised of Loop β6β7, β-strand 7 and Loop β7β8 (Regions 13, 14 and 15, respectively).
|
| Region 14 | | Type: | Ordered | | Name: | β-strand 7 (EF) | | Location: | 511 - 514 | | Length: | 4 | | Region sequence: |
DLVW | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Loop (EF) is comprised of Loop β6β7, β-strand 7 and Loop β7β8 (Regions 13, 14 and 15, respectively).
|
| Region 15 | | Type: | Disordered | | Name: | Loop β7β8 (EF) | | Location: | 515 - 524 | | Length: | 10 | | Region sequence: |
KAQNTWGCGN | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:According to Krimm et al (2002), hydrophobic residue W520 is likely important for "structuring and positioning of Loop β7β8." Solvent-exposed residue C522 exhibits a high degree of mobility.
Loop (EF) is comprised of Loop β6β7, β-strand 7 and Loop β7β8 (Regions 13, 14 and 15, respectively).
|
| Region 16 | | Type: | Ordered | | Name: | β-strand 8 (F) | | Location: | 525 - 531 | | Length: | 7 | | Region sequence: |
SLRTALI | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Krimm et al (2002) describe two classic β-bulges, one involving E443, E444 and R453, the other involving I531, V538 and A539.
|
| Region 17 | | Type: | Disordered | | Name: | Loop β8β9 (FG) | | Location: | 532 - 536 | | Length: | 5 | | Region sequence: |
NSTGE | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Loop β8β9 (FG) contains a turn at N532-G535.
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| Region 18 | | Type: | Ordered | | Name: | β-strand 9 (G) | | Location: | 537 - 544 | | Length: | 8 | | Region sequence: |
EVAMRKLV | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:Krimm et al (2002) describe two classic β-bulges, one involving E443, E444 and R453, the other involving I531, V538 and A539.
|
| Region 19 | | Type: | Disordered | | Name: | C-terminal of C-domain | | Location: | 545 - 553 | | Length: | 9 | | Region sequence: |
RSVTVVEDD | | Modification type: | Fragment
Monomeric
| | PDB: | 1IVT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Unknown
| | Functional subclasses: | Protein-DNA binding
Protein-protein binding
Unknown
| Detection methods:
- Nuclear magnetic resonance (NMR) (303 K; pH: 6.3; 90% H2O, 10% D2O; DTT 2 mM; EDTA 1 mM; Lamin A/C (0.1-1.0mM); NaN3 0.1 mM; Phosphate (buffer) 20 mM)
- Analytical ultracentrifugation (303 K; pH: 6.3; DTT 0.1 mM; Lamin A/C (10-50uM); Sodium phosphate 20 mM)
- Hydrogen-deuterium exchange (by NMR)
| References:
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
| Comments:
|
| References |
- Dhe-Paganon S, Werner ED, Chi YI, Shoelson SE. "Structure of the globular tail of nuclear lamin." J. Biol. Chem.. 2002; 277(20): 17381-4. PubMed: 11901143
- Krimm I, Ostlund C, Gilquin B, Couprie J, Hossenlopp P, Mornon JP, Bonne G, Courvalin JC, Worman HJ, Zinn-Justin S. "The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy." Structure. 2002; 10(6): 811-23. PubMed: 12057196
|
| Comments |
Regions 1-19 of DP00716_C001:Lamin A/C describe the C-domain and are here characterized by Krimm et al (2002). Nine β-strands and eight loops form two β-sheets that sit at a 45-degree angle to each other in a β-sandwich.
The C-domain adopts a classical Ig fold type s, using seven of the β-strands; two additional β-strands are typical of a lamin fold. The N-terminal and C-terminal segments of the C-domain are unstructured and both are situated at the ‘top’ of the structure. Region names include the standard Ig fold convention of single-letter designation for strands and two-letter designation for loops between strands, i.e. β-strand 2(A) and Loop β2β3(AB). Lamin-fold β-strand 1 and Loop β1β2 do not receive Ig fold designations. Lamin-fold β-strand 7, which runs parallel to β-strand 6(E), is designated as part of Ig fold Loop (EF). Loop (EF) is comprised of Loop β6β7, β-strand 7 and Loop β7β8 (Regions 13, 14 and 15, respectively).
β-sheet 1 contains β-strands 1, 4(C), 5(C'), 8(F) and 9(G). β-sheet 2 contains β-strands 2(A), 3(B), 6(E) and 7. Loops β2β3(AB), β4β5(CC') and (EF) are situated together at the ‘top’, and are highly dynamic. Loops β3β4(BC), β5β6(C'E) and β8β9(FG) are situated together at the ‘bottom’ and are far less mobile.
See each region’s comments for more information.
Crystal structure of Lamin A/C C-domain from Dhe-Paganon et al (2002), PDB 1IFR, and NMR solution structure from Krimm et al (2002), PDB 1IVT, are in substantial agreement.
AV sent on 7/13/2011 (PMID:12057196)
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