4gk5
From Proteopedia
Crystal structure of human Rev3-Rev7-Rev1-Polkappa complex
Structural highlights
FunctionMD2L2_HUMAN Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.[1] [2] [3] [4] [5] Publication Abstract from PubMedIn addition to DNA repair pathways, cells utilize translesion DNA synthesis (TLS) to bypass DNA lesions during replication. During TLS, Y-family DNA polymerase (Poleta, Polkappa, Poli and Rev1) inserts specific nucleotide opposite preferred DNA lesions, and then Polzeta consisting of two subunits, Rev3 and Rev7, carries out primer extension. Here, we report the complex structures of Rev3-Rev7-Rev1(CTD) and Rev3-Rev7-Rev1(CTD)-Polkappa(RIR). These two structures demonstrate that Rev1(CTD) contains separate binding sites for Polkappa and Rev7. Our BIAcore experiments provide additional support for the notion that the interaction between Rev3 and Rev7 increases the affinity of Rev7 and Rev1. We also verified through FRET experiment that Rev1, Rev3, Rev7 and Polkappa form a stable quaternary complex in vivo, thereby suggesting an efficient switching mechanism where the "inserter" polymerase can be immediately replaced by an "extender" polymerase within the same quaternary complex. Structural insights into the assembly of human translesion polymerase complexes.,Xie W, Yang X, Xu M, Jiang T Protein Cell. 2012 Nov;3(11):864-74. doi: 10.1007/s13238-012-2102-x. Epub 2012, Nov 10. PMID:23143872[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Min X | Tao J | Wei X
