4MQV

Crystal complex of Rpa32c and Smarcal1 N-terminus

Summary for 4MQV

• Entry DOI: 10.2210/pdb4mqv/pdb
• Descriptor: Replication protein A 32 kDa subunit, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (3 entities in total)
• Functional Keywords: winged hth fold, protein binding, nucleus
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P15927 Q9NZC9
• Total number of polymer chains: 4
• Total formula weight: 21564.27

Authors

Xie, S.,Qian, C.M. (deposition date: 2013-09-16, release date: 2014-07-02, Last modification date: 2024-10-30)

Primary citation

Xie, S.,Lu, Y.,Jakoncic, J.,Sun, H.,Xia, J.,Qian, C.M.
Structure of RPA32 bound to the N-terminus of SMARCAL1 redefines the binding interface between RPA32 and its interacting proteins
Febs J., 281:3382-3396, 2014

PubMed Abstract: Replication 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 α-helical conformation with the highly conserved 11 residues aligned on one face of the α-helix showing extensive interactions with the RPA32C domain. Extensive mutagenesis experiments were performed to corroborate the interactions observed in crystal structure. Moreover, the α1/α2 loop of the RPA32C domain undergoes a conformational rearrangement upon SMARCAL1N binding. NMR study has further confirmed that the RPA32C-SMARCAL1N interaction induces conformational changes in RPA32C. Isothermal titration calorimetry studies have also demonstrated that the conserved α-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.

PubMed: 24910198
DOI: 10.1111/febs.12867

Experimental method

X-RAY DIFFRACTION (1.95 Å)