4mqv | pdb_00004mqv
Crystal complex of Rpa32c and Smarcal1 N-terminus
Structural highlights
Disease[SMAL1_HUMAN] Schimke immuno-osseous dysplasia. The disease is caused by mutations affecting the gene represented in this entry. Function[RFA2_HUMAN] Required for DNA recombination, repair and replication. The activity of RP-A is mediated by single-stranded DNA binding and protein interactions. Required for the efficient recruitment of the DNA double-strand break repair factor RAD51 to chromatin in response to DNA damage.[1] [2] [3] [4] Functions as component of the alternative replication protein A complex (aRPA). aRPA binds single-stranded DNA and probably plays a role in DNA repair; it does not support chromosomal DNA replication and cell cycle progression through S-phase. In vitro, aRPA cannot promote efficient priming by DNA polymerase alpha but supports DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange.[5] [6] [7] [8] [SMAL1_HUMAN] ATP-dependent annealing helicase that catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA). Acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, that unwind DNA.[9] Publication Abstract from PubMedReplication protein A subunit RPA32 contains a C-terminal domain that interacts with a variety of DNA damage response proteins including SMARCAL1, Tipin, UNG2 and XPA. We have solved the high-resolution crystal structure of RPA32 C-terminal domain (RPA32C) in complex with a 26-amino acid peptide derived from the N-terminus of SMARCAL1 (SMARCAL1N). The RPA32C-SMARCAL1N structure reveals a 1:1 binding stoichiometry and displays a well-ordered binding interface. SMARCAL1N adopts a long alpha-helical conformation with the highly conserved 11 residues aligned on one face of the alpha helix showing extensive interactions with the RPA32C domain. Extensive mutagenesis experiments were performed to corroborate the interactions observed in crystal structure. Moreover, the alpha1/alpha2 loop of RPA32C domain undergoes a conformational rearrangement upon SMARCAL1N binding. NMR study has further confirmed that the RPA32C-SMARCAL1N interaction induces the conformational changes in RPA32C. ITC studies have also demonstrated that the conserved alpha-helical motif defined in the current study is required for sufficient binding of RPA32C. Taken together, our study has provided convincing structural information that redefines the common recognition pattern shared by RPA32C interacting proteins. This article is protected by copyright. All rights reserved. Structure of RPA32 bound to N-terminus of SMARCAL1 redefines the binding interface between RPA32 and its interacting proteins.,Xie S, Lu Y, Jakoncic J, Sun H, Xia J, Qian C FEBS J. 2014 Jun 9. doi: 10.1111/febs.12867. PMID:24910198[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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