气候变化领域集成服务门户(CCPortal): SDS22 selectively recognizes and traps metal-deficient inactive PP1

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DOI	10.1073/pnas.1908718116
	SDS22 selectively recognizes and traps metal-deficient inactive PP1
	Choy M.S.; Moon T.M.; Ravindran R.; Bray J.A.; Robinson L.C.; Archuleta T.L.; Shi W.; Peti W.; Tatchell K.; Page R.
发表日期	2019
ISSN	0027-8424
起始页码	20472
结束页码	20481
卷号	116 期号:41
英文摘要	The metalloenzyme protein phosphatase 1 (PP1), which is responsible for ≥50% of all dephosphorylation reactions, is regulated by scores of regulatory proteins, including the highly conserved SDS22 protein. SDS22 has numerous diverse functions, surprisingly acting as both a PP1 inhibitor and as an activator. Here, we integrate cellular, biophysical, and crystallographic studies to address this conundrum. We discovered that SDS22 selectively binds a unique conformation of PP1 that contains a single metal (M2) at its active site, i.e., SDS22 traps metal-deficient inactive PP1. Furthermore, we showed that SDS22 dissociation is accompanied by a second metal (M1) being loaded into PP1, as free metal cannot dissociate the complex and M1-deficient mutants remain constitutively trapped by SDS22. Together, our findings reveal that M1 metal loading and loss are essential for PP1 regulation in cells, which has broad implications for PP1 maturation, activity, and holoenzyme subunit exchange. © 2019 National Academy of Sciences. All rights reserved.
英文关键词	Crystal structure; Inhibitor; Metal binding; Protein phosphatase 1 (PP1); SDS22
语种	英语
scopus关键词	cell protein; phosphoprotein phosphatase 1; SDS22 protein; unclassified drug; Article; binding affinity; binding site; biogenesis; biophysics; catalysis; controlled study; crystallography; enzyme regulation; enzyme specificity; immunoblotting; in vivo study; nonhuman; polyacrylamide gel electrophoresis; priority journal; protein aggregation; protein conformation; protein expression; protein interaction
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160408
作者单位	Choy, M.S., Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Moon, T.M., Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Ravindran, R., Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, United States; Bray, J.A., Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Robinson, L.C., Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, United States; Archuleta, T.L., Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Shi, W., Department of Energy and Photon Sciences, Brookhaven National Laboratory, Upton, NY 11973, United States; Peti, W., Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Tatchell, K., Department of Biochemis...
推荐引用方式 GB/T 7714	Choy M.S.,Moon T.M.,Ravindran R.,et al. SDS22 selectively recognizes and traps metal-deficient inactive PP1[J],2019,116(41).
APA	Choy M.S..,Moon T.M..,Ravindran R..,Bray J.A..,Robinson L.C..,...&Page R..(2019).SDS22 selectively recognizes and traps metal-deficient inactive PP1.Proceedings of the National Academy of Sciences of the United States of America,116(41).
MLA	Choy M.S.,et al."SDS22 selectively recognizes and traps metal-deficient inactive PP1".Proceedings of the National Academy of Sciences of the United States of America 116.41(2019).