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8sok

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Current revision

Cryo-EM structure of human CST bound to POT1(ESDL)/TPP1 in the presence of telomeric ssDNA

Structural highlights

8sok is a 6 chain structure with sequence from Enterovirus A71, Escherichia coli O157:H7, Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.1Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CTC1_HUMAN Coats plus syndrome;Dyskeratosis congenita. The disease is caused by mutations affecting the gene represented in this entry.

Function

CTC1_HUMAN Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill-in during late S/G2 phase (By similarity).[UniProtKB:Q5SUQ9]^[1] ^[2] ^[3] ^[4] ^[5] MALE_ECO57 Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity).

Publication Abstract from PubMed

CST-Polalpha/Primase maintains telomeres through fill-in synthesis of the C-rich telomeric DNA. We report cryo-EM structures that reveal how human CST is recruited to telomeres by the shelterin subunits POT1 and TPP1. CST-POT1/TPP1 is formed through interactions between POT1 and the Ctc1 subunit of CST. Coats plus syndrome mutations map to the POT1-Ctc1 interface, providing mechanistic insights into this disease. CST-POT1/TPP1 is compatible with the previously reported inactive recruitment complex of CST-Polalpha/Primase but not with the distinct conformation of active CST-Polalpha/Primase. We propose that shelterin both recruits and regulates CST-Polalpha/Primase. Structural and biochemical data indicate that this regulation involves phosphorylation of POT1, which promotes CST-POT1/TPP1 interaction and recruitment, whereas POT1 dephosphorylation releases CST-Polalpha/Primase for fill-in synthesis. ONE-SENTENCE SUMMARY: Cryo-EM structures reveal how telomere maintenance factors are recruited and regulated by the shelterin complex.

Structural basis of CST-Polalpha/Primase recruitment and regulation by POT1 at telomeres.,Cai SW, Takai H, Walz T, de Lange T bioRxiv. 2023 May 9:2023.05.08.539880. doi: 10.1101/2023.05.08.539880. Preprint. PMID:37215005^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Miyake Y, Nakamura M, Nabetani A, Shimamura S, Tamura M, Yonehara S, Saito M, Ishikawa F. RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol Cell. 2009 Oct 23;36(2):193-206. PMID:19854130 doi:S1097-2765(09)00587-5
↑ Surovtseva YV, Churikov D, Boltz KA, Song X, Lamb JC, Warrington R, Leehy K, Heacock M, Price CM, Shippen DE. Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Mol Cell. 2009 Oct 23;36(2):207-18. PMID:19854131 doi:http://dx.doi.org/S1097-2765(09)00675-3
↑ Chen LY, Redon S, Lingner J. The human CST complex is a terminator of telomerase activity. Nature. 2012 Aug 23;488(7412):540-4. doi: 10.1038/nature11269. PMID:22763445 doi:http://dx.doi.org/10.1038/nature11269
↑ Stewart JA, Wang F, Chaiken MF, Kasbek C, Chastain PD 2nd, Wright WE, Price CM. Human CST promotes telomere duplex replication and general replication restart after fork stalling. EMBO J. 2012 Aug 29;31(17):3537-49. doi: 10.1038/emboj.2012.215. Epub 2012 Aug 3. PMID:22863775 doi:http://dx.doi.org/10.1038/emboj.2012.215
↑ Wang F, Stewart J, Price CM. Human CST abundance determines recovery from diverse forms of DNA damage and replication stress. Cell Cycle. 2014;13(22):3488-98. doi: 10.4161/15384101.2014.964100. PMID:25483097 doi:http://dx.doi.org/10.4161/15384101.2014.964100
↑ Cai SW, Takai H, Walz T, de Lange T. Structural basis of CST-Polα/Primase recruitment and regulation by POT1 at telomeres. bioRxiv. 2023 May 9:2023.05.08.539880. PMID:37215005 doi:10.1101/2023.05.08.539880

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8sok"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8sok]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterovirus_A71 Enterovirus A71], [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SOK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8sok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sok OCA], [https://pdbe.org/8sok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sok RCSB], [https://www.ebi.ac.uk/pdbsum/8sok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sok ProSAT]</span></td></tr>
 </table>

8sok

From Proteopedia

Current revision

Cryo-EM structure of human CST bound to POT1(ESDL)/TPP1 in the presence of telomeric ssDNA

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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