5iy4
From Proteopedia
Crystal structure of human PCNA in complex with the PIP box of DVC1
Structural highlights
DiseaseSPRTN_HUMAN Progeroid features-hepatocellular carcinoma predisposition syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionSPRTN_HUMAN Regulator of UV-induced DNA damage response: acts as a 'reader' of ubiquitinated PCNA that enhances RAD18-mediated PCNA ubiquitination and translesion DNA synthesis (TLS). Recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis. Acts as a regulator of TLS by recruiting VCP/p97 to sites of DNA damage, possibly leading to extraction of DNA polymerase eta (POLH) by VCP/p97 to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedIn higher eukaryotes, DVC1 (SPRTN, Spartan or C1orf124) is implicated in the translesion synthesis (TLS) pathway. DVC1 localizes to sites of DNA damage, binds to the proliferating cell nuclear antigen (PCNA) via its conserved PCNA-interacting motif (PIP box), and associates with ubiquitin selective segregase p97 and other factors, thus regulating translesion synthesis polymerases. Here, we report the crystal structure of human PCNA in complex with a peptide ((321)SNSHQNVLSNYFPRVS(336)) derived from human DVC1 that contains a unique YF type PIP box. Structural analysis reveals the detailed PIP box-PCNA interaction. Interestingly, substitution of Y331 with Phe severely reduces its PCNA binding affinity. These findings offer new insights into the determinants of PIP box for PCNA binding. Crystal structure of human PCNA in complex with the PIP box of DVC1.,Wang Y, Xu M, Jiang T Biochem Biophys Res Commun. 2016 May 27;474(2):264-70. doi:, 10.1016/j.bbrc.2016.04.053. Epub 2016 Apr 13. PMID:27084448[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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