General information | DisProt: | DP00533 | Name: | Regulatory protein SIR3 | Synonym(s): | SIR3_YEAST
Silent information regulator 3
| First appeared in release: | Release 6.00 (07/01/2012) | UniProt: | P06701 | UniGene: | | SwissProt: | SIR3_YEAST | TrEMBL: | | NCBI (GI): | 1711392 | Source organism: | Saccharomyces cerevisiae (Baker's yeast) | Sequence length: | 978 | Percent disordered: | 34% | Homologues: | |
Native sequence |
10 20 30 40 50 60 | | | | | | MAKTLKDLDG WQVIITDDQG RVIDDNNRRR SRKRGGENVF LKRISDGLSF GKGESVIFND - 60 NVTETYSVYL IHEIRLNTLN NVVEIWVFSY LRWFELKPKL YYEQFRPDLI KEDHPLEFYK - 120 DKFFNEVNKS ELYLTAELSE IWLKDFIAVG QILPESQWND SSIDKIEDRD FLVRYACEPT - 180 AEKFVPIDIF QIIRRVKEME PKQSDEYLKR VSVPVSGQKT NRQVMHKMGV ERSSKRLAKK - 240 PSMKKIKIEP SADDDVNNGN IPSQRGTSTT HGSISPQEES VSPNISSASP SALTSPTDSS - 300 KILQKRSISK ELIVSEEIPI NSSEQESDYE PNNETSVLSS KPGSKPEKTS TELVDGRENF - 360 VYANNPEVSD DGGLEEETDE VSSESSDEAI IPVNKRRGAH GSELSSKIRK IHIQETQEFS - 420 KNYTTETDNE MNGNGKPGIP RGNTKIHSMN ENPTPEKGNA KMIDFATLSK LKKKYQIILD - 480 RFAPDNQVTD SSQLNKLTDE QSSLDVAGLE DKFRKACSSS GRETILSNFN ADINLEESIR - 540 ESLQKRELLK SQVEDFTRIF LPIYDSLMSS QNKLFYITNA DDSTKFQLVN DVMDELITSS - 600 ARKELPIFDY IHIDALELAG MDALYEKIWF AISKENLCGD ISLEALNFYI TNVPKAKKRK - 660 TLILIQNPEN LLSEKILQYF EKWISSKNSK LSIICVGGHN VTIREQINIM PSLKAHFTEI - 720 KLNKVDKNEL QQMIITRLKS LLKPFHVKVN DKKEMTIYNN IREGQNQKIP DNVIVINHKI - 780 NNKITQLIAK NVANVSGSTE KAFKICEAAV EISKKDFVRK GGLQKGKLVV SQEMVPRYFS - 840 EAINGFKDET ISKKIIGMSL LMRTFLYTLA QETEGTNRHT LALETVLIKM VKMLRDNPGY - 900 KASKEIKKVI CGAWEPAITI EKLKQFSWIS VVNDLVGEKL VVVVLEEPSA SIMVELKLPL - 960 EINYAFSMDE EFKNMDCI
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Functional narrative |
The silent information regulator protein 3 (Sir3p) functions in the initiation, propagation, and maintenance of transcriptionally silenced chromatin in Saccharomyces cerevisiae. The Sir3p monomer has a unique tripartite domain organization, including a stretch of nearly 300 residues that are intrinsically disordered, which lie internal to the structured N- and C-terminal regions. The proteins SIR1 through SIR4 are required for transcriptional repression of the silent mating type loci, HML and HMR. The proteins SIR2 through SIR4 repress mulitple loci by modulating chromatin structure. Involves the compaction of chromatin fiber into a more condensed form.
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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: | Ordered | Name: | N-terminal region | Location: | 1 - 215 | Length: | 215 | Region sequence: |
MAKTLKDLDGWQVIITDDQGRVIDDNNRRRSRKRGGENVFLKRISDGLSFGKGESVIFND NVTETYSVYLIHEIRLNTLNNVVEIWVFSYLRWFELKPKLYYEQFRPDLIKEDHPLEFYK DKFFNEVNKSELYLTAELSEIWLKDFIAVGQILPESQWNDSSIDKIEDRDFLVRYACEPT AEKFVPIDIFQIIRRVKEMEPKQSDEYLKRVSVPV | Modification type: | Engineered
Fragment
Native
| PDB: | 2FL7:A, 2FVU:A, 3TU4:K | Structural/functional type: | Function arises from the ordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Intraprotein interaction
Protein-DNA binding
Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (293 K; Sir3p 1 uM; NaCl 0.5 M; GuHCl)
- Sensitivity to proteolysis (Trypsin)
- Analytical ultracentrifugation (294 K; )
- X-ray crystallography (298 K; pH: 6.5; 1) NTD of Sir3p (aa 1-229) (PDB 2FL7); HEPES 0.1 M; NaCl 200 mM; PEG400 (10%))
- X-ray crystallography (290 K; pH: 3.75; 1) NTD of Sir3p (aa 1-218) (PDB 2FVU); sodium formate 4 M)
- X-ray crystallography (294 K; pH: 7; 1) NTD of Sir3p (aa 1-213) (PDB 3TU4); nucleosome core particle (NCP) (in complex))
| References:
- Armache KJ, Garlick JD, Canzio D, Narlikar GJ, Kingston RE. "Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution." Science. 2011; 334(6058): 977-82. PubMed: 22096199
- Connelly JJ, Yuan P, Hsu HC, Li Z, Xu RM, Sternglanz R. "Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain." Mol. Cell. Biol.. 2006; 26(8): 3256-65. PubMed: 16581798
- Hou Z, Danzer JR, Fox CA, Keck JL. "Structure of the Sir3 protein bromo adjacent homology (BAH) domain from S. cerevisiae at 1.95 A resolution." Protein Sci.. 2006; 15(5): 1182-6. PubMed: 16641491
- McBryant SJ, Krause C, Hansen JC. "Domain Organization and Quaternary Structure of the Saccharomyces cerevisiae Silent Information Regulator 3 Protein, Sir3p." Biochemistry. 2006; 45(51): 15941-8. PubMed: 17176117
| Comments:N-terminal region contains the bromo adjacent homology (BAH) domain at ~aa L48-D188.
Experiments by McBryant et al (2006), (CD, proteolysis, analytical centrifugation) were performed using recombinant Sir3p.
PDB 2FL7 is from Hou et al (2006), PDB 2FVU is from Connelly et al (2006), PDB 3TU4 is in complex with NCP and is from Armache et al (2011).
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Region 2 | Type: | Disordered | Name: | central disordered region | Location: | 216 - 550 | Length: | 335 | Region sequence: |
SGQKTNRQVMHKMGVERSSKRLAKKPSMKKIKIEPSADDDVNNGNIPSQRGTSTTHGSIS PQEESVSPNISSASPSALTSPTDSSKILQKRSISKELIVSEEIPINSSEQESDYEPNNET SVLSSKPGSKPEKTSTELVDGRENFVYANNPEVSDDGGLEEETDEVSSESSDEAIIPVNK RRGAHGSELSSKIRKIHIQETQEFSKNYTTETDNEMNGNGKPGIPRGNTKIHSMNENPTP EKGNAKMIDFATLSKLKKKYQIILDRFAPDNQVTDSSQLNKLTDEQSSLDVAGLEDKFRK ACSSSGRETILSNFNADINLEESIRESLQKRELLK | Modification type: | Engineered
Native
| PDB: | 3OWT:C | Structural/functional type: | Function arises from the disordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Intraprotein interaction
Protein-DNA binding
Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (293 K; GuHCl; NaCl 0.5 M; Sir3p 1 uM)
- Sensitivity to proteolysis (Trypsin)
- Analytical ultracentrifugation (294 K; )
- X-ray crystallography (277 K; pH: 4.8; 1) Sir3p fragment (aa 456-481) (PDB 3OWT); ammonium acetate 200 mM; DTT 10 mm; PEG4K (30%); RAP1 fragment (aa 672-827) (in complex); sodium citrate 100 mM)
| References:
- Chen Y, Rai R, Zhou ZR, Kanoh J, Ribeyre C, Yang Y, Zheng H, Damay P, Wang F, Tsujii H, Hiraoka Y, Shore D, Hu HY, Chang S, Lei M. "A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms." Nat. Struct. Mol. Biol.. 2011; 18(2): 213-21. PubMed: 21217703
- McBryant SJ, Krause C, Hansen JC. "Domain Organization and Quaternary Structure of the Saccharomyces cerevisiae Silent Information Regulator 3 Protein, Sir3p." Biochemistry. 2006; 45(51): 15941-8. PubMed: 17176117
| Comments:Experiments by McBryant et al (2006), (CD, proteolysis, analytical centrifugation) were performed using recombinant Sir3p.
According to McBryant et al (2006), the central region is "largely disordered, including two long stretches (residues 220-275 and 325-475) that are predicted to almost completely lack order." Additionally, they note this central region contains "islands of order."
PDB structure 3OWT, chain C, from Chen et al (2011), contains a small fragment of the central region comprising the RAP1-interaction motif (E456-R481) in complex with DNA-binding protein RAP1.
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Region 3 | Type: | Ordered | Name: | C-terminal region | Location: | 551 - 978 | Length: | 428 | Region sequence: |
SQVEDFTRIFLPIYDSLMSSQNKLFYITNADDSTKFQLVNDVMDELITSSARKELPIFDY IHIDALELAGMDALYEKIWFAISKENLCGDISLEALNFYITNVPKAKKRKTLILIQNPEN LLSEKILQYFEKWISSKNSKLSIICVGGHNVTIREQINIMPSLKAHFTEIKLNKVDKNEL QQMIITRLKSLLKPFHVKVNDKKEMTIYNNIREGQNQKIPDNVIVINHKINNKITQLIAK NVANVSGSTEKAFKICEAAVEISKKDFVRKGGLQKGKLVVSQEMVPRYFSEAINGFKDET ISKKIIGMSLLMRTFLYTLAQETEGTNRHTLALETVLIKMVKMLRDNPGYKASKEIKKVI CGAWEPAITIEKLKQFSWISVVNDLVGEKLVVVVLEEPSASIMVELKLPLEINYAFSMDE EFKNMDCI | Modification type: | Engineered
Native
| PDB: | 3TE6:A | Structural/functional type: | Function arises from the ordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Intraprotein interaction
Protein-DNA binding
Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (293 K; GuHCl; NaCl 0.5 M; Sir3p 1 uM)
- Sensitivity to proteolysis (Trypsin)
- Analytical ultracentrifugation (294 K; )
- X-ray crystallography (277 K; pH: 7.5; 1) Sir3p fragment (aa 530-845) (PDB 3TE6); ammonium sulfate 2 M; HEPES 0.1 M; PEG 400 (2% (w/v)))
| References:
- Ehrentraut S, Hassler M, Oppikofer M, Kueng S, Weber JM, Mueller JW, Gasser SM, Ladurner AG, Ehrenhofer-Murray AE. "Structural basis for the role of the Sir3 AAA+ domain in silencing: interaction with Sir4 and unmethylated histone H3K79." Genes Dev.. 2011; 25(17): 1835-46. PubMed: 21896656
- McBryant SJ, Krause C, Hansen JC. "Domain Organization and Quaternary Structure of the Saccharomyces cerevisiae Silent Information Regulator 3 Protein, Sir3p." Biochemistry. 2006; 45(51): 15941-8. PubMed: 17176117
| Comments:Experiments by McBryant et al (2006), (CD, proteolysis, analytical centrifugation) were performed using recombinant Sir3p.
PDB structure 3TE6, from Ehrentraut et al (2011), shows the AAA+ ATPase-like domain (N530-G845).
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References |
- Adkins NL, McBryant SJ, Johnson CN, Leidy JM, Woodcock CL, Robert CH, Hansen JC, Georgel PT. "Role of nucleic acid binding in Sir3p-dependent interactions with chromatin fibers." Biochemistry. 2009; 48(2): 276-88. PubMed: 19099415
- McBryant SJ, Krause C, Hansen JC. "Domain Organization and Quaternary Structure of the Saccharomyces cerevisiae Silent Information Regulator 3 Protein, Sir3p." Biochemistry. 2006; 45(51): 15941-8. PubMed: 17176117
- McBryant SJ, Krause C, Woodcock CL, Hansen JC. "The silent information regulator 3 protein, SIR3p, binds to chromatin fibers and assembles a hypercondensed chromatin architecture in the presence of salt." Mol. Cell. Biol.. 2008; 28(11): 3563-72. PubMed: 18362167
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Comments |
Regions 1-3 are delineated by McBryant et al (2006). Additional discussion of Sir3p-chromatin interactions is found in McBryant et al (2008) and Adkins et al (2009).
AV sent 6/19/2012 (PMID:17176117)
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