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复制蛋白 A 对 DNA 损伤反应蛋白 SMARCAL1 的募集的结构分析。

Structural analysis of replication protein A recruitment of the DNA damage response protein SMARCAL1.

机构信息

Department of Biochemistry, ‡Department of Biological Sciences, §Department of Chemistry, and ∥Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.

出版信息

Biochemistry. 2014 May 13;53(18):3052-61. doi: 10.1021/bi500252w. Epub 2014 Apr 30.

DOI:10.1021/bi500252w
PMID:24730652
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4020579/
Abstract

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 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 circular dichroism spectroscopy revealed that RPA32C binds SMARCAL1-RBM with a Kd of 2.5 μM and induces a disorder-to-helix transition. The crystal structure of RPA32C was refined to 1.4 Å resolution, and the SMARCAL1-RBM binding site was mapped on the structure on the basis of nuclear magnetic resonance chemical shift perturbations. Conservation of the interaction surface to other RBM-containing proteins allowed 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.

摘要

SWI/SNF 相关、基质相关、肌动蛋白依赖的染色质调节子亚家族 A 样蛋白 1（SMARCAL1）是一种新发现的参与重塑停滞复制叉的 DNA 损伤反应蛋白。真核单链 DNA 结合蛋白复制蛋白 A（RPA）在体内将 SMARCAL1 招募到停滞的叉上，并促进含有前导链缺口的叉的回归。这两种活性都由 SMARCAL1 氨基末端的 RPA 结合基序（RBM）和 RPA32 kDa 亚基（RPA32C）的 C 末端翼状螺旋结构域之间的直接相互作用介导。在这里，我们报告了 SMARCAL1-RPA 相互作用的生物物理和结构特征。等温滴定量热法和圆二色性光谱显示，RPA32C 以 2.5 μM 的 Kd 结合 SMARCAL1-RBM，并诱导无规卷曲到螺旋的转变。RPA32C 的晶体结构被细化到 1.4 Å 分辨率，并且根据核磁共振化学位移扰动将 SMARCAL1-RBM 结合位点映射到结构上。与其他含有 RBM 的蛋白质相互作用表面的保守性允许构建 RPA32C/SMARCAL1-RBM 复合物的模型。我们的结果的意义是讨论了 SMARCAL1 和其他 DNA 损伤反应和修复蛋白被招募到停滞的复制叉上的情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/02f5790fe440/bi-2014-00252w_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/173059a79b07/bi-2014-00252w_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/f1ea70a909c8/bi-2014-00252w_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/17ad6916fd4e/bi-2014-00252w_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/c71a03bd216e/bi-2014-00252w_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/101307f6d48f/bi-2014-00252w_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/58ff48b25eba/bi-2014-00252w_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/75fc771501ef/bi-2014-00252w_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/b5d5bf0b5cd7/bi-2014-00252w_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/ed586321d7d0/bi-2014-00252w_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/02f5790fe440/bi-2014-00252w_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/173059a79b07/bi-2014-00252w_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/f1ea70a909c8/bi-2014-00252w_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/17ad6916fd4e/bi-2014-00252w_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/c71a03bd216e/bi-2014-00252w_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/101307f6d48f/bi-2014-00252w_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/58ff48b25eba/bi-2014-00252w_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/75fc771501ef/bi-2014-00252w_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/b5d5bf0b5cd7/bi-2014-00252w_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/ed586321d7d0/bi-2014-00252w_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/4020579/02f5790fe440/bi-2014-00252w_0007.jpg

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3
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4
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