气候变化领域集成服务门户(CCPortal): Competing stress-dependent oligomerization pathways regulate self-assembly of the periplasmic protease-chaperone DegP

CCPortal

DOI	10.1073/pnas.2109732118
	Competing stress-dependent oligomerization pathways regulate self-assembly of the periplasmic protease-chaperone DegP
	Harkness R.W.; Toyama Y.; Ripstein Z.A.; Zhao H.; Sever A.I.M.; Luan Q.; Brady J.P.; Clark P.L.; Schuck P.; Kay L.E.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:32
英文摘要	DegP is an oligomeric protein with dual protease and chaperone activity that regulates protein homeostasis and virulence factor trafficking in the periplasm of gram-negative bacteria. A number of oligomeric architectures adopted by DegP are thought to facilitate its function. For example, DegP can form a "resting" hexamer when not engaged to substrates, mitigating undesired proteolysis of cellular proteins. When bound to substrate proteins or lipid membranes, DegP has been shown to populate a variety of cageor bowl-like oligomeric states that have increased proteolytic activity. Though a number of DegP's substrate-engaged structures have been robustly characterized, detailed mechanistic information underpinning its remarkable oligomeric plasticity and the corresponding interplay between these dynamics and biological function has remained elusive. Here, we have used a combination of hydrodynamics and NMR spectroscopy methodologies in combination with cryogenic electron microscopy to shed light on the apo-DegP selfassembly mechanism. We find that, in the absence of bound substrates, DegP populates an ensemble of oligomeric states, mediated by self-assembly of trimers, that are distinct from those observed in the presence of substrate. The oligomeric distribution is sensitive to solution ionic strength and temperature and is shifted toward larger oligomeric assemblies under physiological conditions. Substrate proteins may guide DegP toward canonical cage-like structures by binding to these preorganized oligomers, leading to changes in conformation. The properties of DegP self-assembly identified here suggest that apo-DegP can rapidly shift its oligomeric distribution in order to respond to a variety of biological insults. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Hydrodynamics; Methyl-TROSY NMR; Protein self-assembly; Protein thermodynamics and kinetics
语种	英语
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/238833
作者单位	Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada; National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD 20892, United States; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States
推荐引用方式 GB/T 7714	Harkness R.W.,Toyama Y.,Ripstein Z.A.,et al. Competing stress-dependent oligomerization pathways regulate self-assembly of the periplasmic protease-chaperone DegP[J],2021,118(32).
APA	Harkness R.W..,Toyama Y..,Ripstein Z.A..,Zhao H..,Sever A.I.M..,...&Kay L.E..(2021).Competing stress-dependent oligomerization pathways regulate self-assembly of the periplasmic protease-chaperone DegP.Proceedings of the National Academy of Sciences of the United States of America,118(32).
MLA	Harkness R.W.,et al."Competing stress-dependent oligomerization pathways regulate self-assembly of the periplasmic protease-chaperone DegP".Proceedings of the National Academy of Sciences of the United States of America 118.32(2021).