4ou0
From Proteopedia
(Difference between revisions)
| (5 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| + | |||
==Crystal Structure of RPA32C== | ==Crystal Structure of RPA32C== | ||
| - | <StructureSection load='4ou0' size='340' side='right' caption='[[4ou0]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='4ou0' size='340' side='right'caption='[[4ou0]], [[Resolution|resolution]] 1.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[4ou0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OU0 OCA]. < | + | <table><tr><td colspan='2'>[[4ou0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OU0 FirstGlance]. <br> |
| - | <b>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4Å</td></tr> |
| - | <b>[[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene></td></tr> |
| - | <b> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ou0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ou0 OCA], [https://pdbe.org/4ou0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ou0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ou0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ou0 ProSAT]</span></td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[ | + | </table> |
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RFA2_HUMAN 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.<ref>PMID:15205463</ref> <ref>PMID:19116208</ref> <ref>PMID:19996105</ref> <ref>PMID:20154705</ref> 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.<ref>PMID:15205463</ref> <ref>PMID:19116208</ref> <ref>PMID:19996105</ref> <ref>PMID:20154705</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like1 (SMARCAL1) is a recently identified DNA damage response protein involved in remodeling stalled replication forks. The eukaryotic single-strand (ss) DNA-binding protein Replication Protein A (RPA) recruits SMARCAL1 to stalled forks in vivo and facilitates regression of forks containing leading strand gaps. Both activities are mediated by a direct interaction between an RPA-binding motif (RBM) at the N-terminus of SMARCAL1 and the C-terminal winged-helix domain of the RPA 32-kDa subunit (RPA32C). Here we report a biophysical and structural characterization of the SMARCAL1-RPA interaction. Isothermal titration calorimetry and CD spectroscopy revealed that RPA32C binds the SMARCAL1-RBM with a Kd of 3 muM and induces a disorder-to-helix transition. The crystal structure of RPA32C was refined to 1.4 A resolution and the SMARCAL1-RBM binding site was mapped on the structure on the basis of NMR chemical shift perturbations. Conservation of the interaction surface to other RBM-containing proteins enabled construction of a model for the RPA32C/SMARCAL1-RBM complex. The implications of our results are discussed with respect to the recruitment of SMARCAL1 and other DNA damage response and repair proteins to stalled replication forks. | SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like1 (SMARCAL1) is a recently identified DNA damage response protein involved in remodeling stalled replication forks. The eukaryotic single-strand (ss) DNA-binding protein Replication Protein A (RPA) recruits SMARCAL1 to stalled forks in vivo and facilitates regression of forks containing leading strand gaps. Both activities are mediated by a direct interaction between an RPA-binding motif (RBM) at the N-terminus of SMARCAL1 and the C-terminal winged-helix domain of the RPA 32-kDa subunit (RPA32C). Here we report a biophysical and structural characterization of the SMARCAL1-RPA interaction. Isothermal titration calorimetry and CD spectroscopy revealed that RPA32C binds the SMARCAL1-RBM with a Kd of 3 muM and induces a disorder-to-helix transition. The crystal structure of RPA32C was refined to 1.4 A resolution and the SMARCAL1-RBM binding site was mapped on the structure on the basis of NMR chemical shift perturbations. Conservation of the interaction surface to other RBM-containing proteins enabled construction of a model for the RPA32C/SMARCAL1-RBM complex. The implications of our results are discussed with respect to the recruitment of SMARCAL1 and other DNA damage response and repair proteins to stalled replication forks. | ||
| Line 12: | Line 16: | ||
Structural analysis of RPA recruitment of the DNA damage response protein SMARCAL1.,Feldkamp MD, Mason AC, Eichman BF, Chazin WJ Biochemistry. 2014 Apr 15. PMID:24730652<ref>PMID:24730652</ref> | Structural analysis of RPA recruitment of the DNA damage response protein SMARCAL1.,Feldkamp MD, Mason AC, Eichman BF, Chazin WJ Biochemistry. 2014 Apr 15. PMID:24730652<ref>PMID:24730652</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 4ou0" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Chazin WJ]] |
| - | [[Category: | + | [[Category: Eichman BF]] |
| - | [[Category: | + | [[Category: Feldkamp MD]] |
| - | [[Category: | + | [[Category: Mason AC]] |
| - | + | ||
| - | + | ||
Current revision
Crystal Structure of RPA32C
| |||||||||||
