Structural Evidence for Direct Interactions between the BRCT Domains of Human BRCA1 and a Phospho-peptide from Human ACC1

@article{citeulike:2744283, abstract = {Abstract: The tandem BRCA1 C-terminal (BRCT) domains are phospho-serine/threonine recognition modules essential for the function of BRCA1. Recent studies suggest that acetyl-CoA carboxylase 1 (ACC1), an enzyme with crucial roles in de novo fatty acid biosynthesis and lipogenesis and essential for cancer cell survival, may be a novel binding partner for BRCA1, through interactions with its BRCT domains. We report here the crystal structure at 3.2 \r{A} resolution of human BRCA1 BRCT domains in complex with a phospho-peptide from human ACC1 (p-ACC1 peptide, with the sequence 1258-DSPPQ-pS-PTFPEAGH-1271), which provides molecular evidence for direct interactions between BRCA1 and ACC1. The p-ACC1 peptide is bound in an extended conformation, located in a groove between the tandem BRCT domains. There are recognizable and significant structural differences to the binding modes of two other phospho-peptides to these domains, from BACH1 and CtIP, even though they share a conserved pSer-Pro-(Thr/Val)-Phe motif. Our studies establish a framework for understanding the regulation of lipid biosynthesis by BRCA1 through its inhibition of ACC1 activity, which could be a novel tumor suppressor function of BRCA1.}, address = {Department of Biological Sciences, Columbia University, New York City, New York 10027}, author = {Shen, Yang and Tong, Liang }, citeulike-article-id = {2744283}, doi = {10.1021/bi800314m}, journal = {Biochemistry}, month = {May}, posted-at = {2008-05-02 07:56:46}, priority = {2}, title = {Structural Evidence for Direct Interactions between the BRCT Domains of Human BRCA1 and a Phospho-peptide from Human ACC1}, url = {http://dx.doi.org/10.1021/bi800314m}, year = {2008} }

TY - JOUR ID - citeulike:2744283 L3 - citeulike-article-id:2744283 TI - Structural Evidence for Direct Interactions between the BRCT Domains of Human BRCA1 and a Phospho-peptide from Human ACC1 JF - Biochemistry AD - Department of Biological Sciences, Columbia University, New York City, New York 10027 N2 - Abstract: The tandem BRCA1 C-terminal (BRCT) domains are phospho-serine/threonine recognition modules essential for the function of BRCA1. Recent studies suggest that acetyl-CoA carboxylase 1 (ACC1), an enzyme with crucial roles in de novo fatty acid biosynthesis and lipogenesis and essential for cancer cell survival, may be a novel binding partner for BRCA1, through interactions with its BRCT domains. We report here the crystal structure at 3.2 Å resolution of human BRCA1 BRCT domains in complex with a phospho-peptide from human ACC1 (p-ACC1 peptide, with the sequence 1258-DSPPQ-pS-PTFPEAGH-1271), which provides molecular evidence for direct interactions between BRCA1 and ACC1. The p-ACC1 peptide is bound in an extended conformation, located in a groove between the tandem BRCT domains. There are recognizable and significant structural differences to the binding modes of two other phospho-peptides to these domains, from BACH1 and CtIP, even though they share a conserved pSer-Pro-(Thr/Val)-Phe motif. Our studies establish a framework for understanding the regulation of lipid biosynthesis by BRCA1 through its inhibition of ACC1 activity, which could be a novel tumor suppressor function of BRCA1. AU - Shen, Yang AU - Tong, Liang PY - 2008/05/02/ UR - http://dx.doi.org/10.1021/bi800314m ER -