气候变化领域集成服务门户(CCPortal): Sortase-assembled pili in Corynebacterium diphtheriae are built using a latch mechanism

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DOI	10.1073/pnas.2019649118
	Sortase-assembled pili in Corynebacterium diphtheriae are built using a latch mechanism
	McConnell S.A.; McAllister R.A.; Amer B.R.; Mahoney B.J.; Sue C.K.; Chang C.; Ton-That H.; Clubb R.T.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Gram-positive bacteria assemble pili (fimbriae) on their surfaces to adhere to host tissues and to promote polymicrobial interactions. These hair-like structures, although very thin (1 to 5 nm), exhibit impressive tensile strengths because their protein components (pilins) are covalently crosslinked together via lysine–isopeptide bonds by pilus-specific sortase enzymes. While atomic structures of isolated pilins have been determined, how they are joined together by sortases and how these interpilin crosslinks stabilize pilus structure are poorly understood. Using a reconstituted pilus assembly system and hybrid structural biology methods, we elucidated the solution structure and dynamics of the crosslinked interface that is repeated to build the prototypical SpaA pilus from Corynebacterium diphtheriae. We show that sortase-catalyzed introduction of a K190-T494 isopeptide bond between adjacent SpaA pilins causes them to form a rigid interface in which the LPLTG sorting signal is inserted into a large binding groove. Cellular and quantitative kinetic measurements of the crosslinking reaction shed light onto the mechanism of pilus biogenesis. We propose that the pilus-specific sortase in C. diphtheriae uses a latch mechanism to select K190 on SpaA for crosslinking in which the sorting signal is partially transferred from the enzyme to a binding groove in SpaA in order to facilitate catalysis. This process is facilitated by a conserved loop in SpaA, which after crosslinking forms a stabilizing latch that covers the K190-T494 isopeptide bond. General features of the structure and sortase-catalyzed assembly mechanism of the SpaA pilus are likely conserved in Gram-positive bacteria. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Pili \| sortase \| Gram positive \| lysine isopeptide bond \| integrative structural biology
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/180149
作者单位	Department of Chemistry and Biochemistry, University of California, Los Angeles-US Department of Energy Institute of Genomics and Proteomics, University of California, Los Angeles, CA 90095, United States; Division of Oral Biology and Medicine, University of California, Los Angeles, CA 90095, United States; Molecular Biology Institute, University of California, Los Angeles, CA 90095, United States
推荐引用方式 GB/T 7714	McConnell S.A.,McAllister R.A.,Amer B.R.,et al. Sortase-assembled pili in Corynebacterium diphtheriae are built using a latch mechanism[J],2021,118(12).
APA	McConnell S.A..,McAllister R.A..,Amer B.R..,Mahoney B.J..,Sue C.K..,...&Clubb R.T..(2021).Sortase-assembled pili in Corynebacterium diphtheriae are built using a latch mechanism.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	McConnell S.A.,et al."Sortase-assembled pili in Corynebacterium diphtheriae are built using a latch mechanism".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).