| General information | | DisProt: | DP00710 | | Name: | Immunoglobulin G 1 MAK33 Heavy Chain Fab fragment | | Synonym(s): | IgG1 HC monoclonal antibody MAK33 Fab fragment
| | First appeared in release: | Release 5.7 (02/28/2011) | | UniProt: | N/A | | UniGene: | | | SwissProt: | N/A mouse or rat | | TrEMBL: | | | NCBI (GI): | | | Source organism: | murine | | Sequence length: | 208 | | Percent disordered: | 47% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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SGGGLVKPAG SLKLSCAASG FTFSSYYMYW VRQTPDKRLE WVATISDGGS YTYYPDSVKG - 60
RFTISRDNAK NNLYLQMSSL KSEDTAMYYC ARDAMDYWGQ GTLVTVSAAK TTPPSVYPLA - 120
PGSAAQTNSM VTLGCLVKGY FPEPVTVTWN SGSLSSGVHT FPAVLQSDLY TLSSSVTVPS - 180
STWPSETVTC NVAHPASSTK VDKKIVPR
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| Functional narrative |
Monoclonal antibody MAK33 is of the kappa/IgG1 type, and it inhibits creatine kinase in skeletal muscle (CK-MM). IgG antibody is secreted to perform its antigen-binding functions. Structurally, IgG antibodies, consist of four peptide chains: two identical light chains and two identical heavy chains, linked to form the characteristic Y-shape. Light chain peptide is composed of a variable (VL) domain and a constant (CL) domain. Heavy chain is composed of a variable (VH) domain and three constant (CH1, CH2, CH3) domains. Each upper branch of the Y-shape is a Fab antigen-binding fragment, while the stem is the Fc fragment. A Fab fragment is formed by a light chain in complex with one set of VH and CH1 domains, and the two variable domains (VL and VH) in concert form the antigen-binding site at the top of the branch. The remaining domains (two sets of CH3 and CH4) form the Fc fragment.
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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.
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| Region 1 | | Type: | Disordered | | Name: | CH1 domain | | Location: | 111 - 208 | | Length: | 98 | | Region sequence: |
TTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLY
TLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPR | | Modification type: | Complex
Engineered
Fragment
| | PDB: | 1FH5:H | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- X-ray crystallography (277 K; pH: 5.6; glycerol 16 %; Na citrate; NaCl 1 M; PEG 8k 16 %)
- Circular dichroism (CD) spectroscopy, far-UV (298 K; CH1 domain (in complex with CL domain) 15 uM; CL domain 45 uM; PBS)
- Fluorescence, intrinsic (298 K; CH1 domain 2 uM; CL domain (varying concentrations))
- Fluorescence polarization/anisotropy (298 K; CH1 (varying concentrations); CL domain mutant A113C (lucifer yellow-labelled) 1 uM)
- Nuclear magnetic resonance (NMR) (298 K; CH1 domain (in complex with CL domain); CL domain (2-fold excess))
- Nuclear magnetic resonance (NMR) (286 K; CH1 domain (unfolded))
- Circular dichroism (CD) spectroscopy, far-UV (298 K; CH1 domain 45 uM; PBS)
| References:
- Augustine JG, de La Calle A, Knarr G, Buchner J, Frederick CA. "The crystal structure of the Fab fragment of the monoclonal antibody MAK33. Implications for folding and interaction with the chaperone BiP." J. Biol. Chem.. 2000; 276(5): 3287-94. PubMed: 11036070
- Feige MJ, Groscurth S, Marcinowski M, Shimizu Y, Kessler H, Hendershot LM, Buchner J. "An unfolded CH1 domain controls the assembly and secretion of IgG antibodies." Mol. Cell. 2009; 34(5): 569-79. PubMed: 19524537
| Comments:Augustine et al (2000) produced the PDB structure 1FH5, and it is used as the basis for further work by Feige et al (2009). Amino acid residue numbering for the PDB structure differs from the DisProt record due to non-sequential numbering of the PDB file and certain residues not being resolved in the crystal structure.
According to Feige et al (2009), experiments show the CH1 domain of MAK33 IgG1 Fab fragment is completely disordered, but folds into a "well-defined beta-sheet structure" in the required presence of the CL domain. Further, both Augustine et al (2000) and Feige et al (2009) note that the isomerization of a highly-conserved proline (P142 in DP00710) is critical for CH1 domain folding and subsequent secretion of the assembled IgG molecule.
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| References |
- Augustine JG, de La Calle A, Knarr G, Buchner J, Frederick CA. "The crystal structure of the Fab fragment of the monoclonal antibody MAK33. Implications for folding and interaction with the chaperone BiP." J. Biol. Chem.. 2000; 276(5): 3287-94. PubMed: 11036070
- Feige MJ, Groscurth S, Marcinowski M, Shimizu Y, Kessler H, Hendershot LM, Buchner J. "An unfolded CH1 domain controls the assembly and secretion of IgG antibodies." Mol. Cell. 2009; 34(5): 569-79. PubMed: 19524537
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| Comments |
This protein, IgG1 Heavy Chain MAK33 Fab fragment, does not have a corresponding UniProt entry on which to base the DisProt record, therefore, just the experimental fragment from PDB structure 1FH5 (Augustine et al, 2000) is used in the "General Information" section. Due to non-sequential numbering of the PDB file (and certain unresolved residues in the crystal structure), amino acid residue numbering for the DisProt record differs from PDB.
AV (02/25/2011) PubMed: 19524537
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