4ou0
From Proteopedia
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== 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]. <br> | [[4ou0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OU0 OCA]. <br> | ||
| - | <b>Related:</b> [[1dpu|1dpu]]<br> | + | <b>[[Non-Standard_Residue|NonStd Res:]]</b> <scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene><br> |
| + | <b>[[Related_structure|Related:]]</b> [[1dpu|1dpu]]<br> | ||
<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br> | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br> | ||
| + | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ou0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ou0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ou0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ou0 PDBsum]</span><br> | ||
== 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. | ||
Revision as of 10:04, 30 April 2014
Crystal Structure of RPA32C
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