Structure, substrate recognition and initiation of hyaluronan synthase

doi:10.1038/s41586-022-04534-2

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	Structure, substrate recognition and initiation of hyaluronan synthase
	Maloney, Finn P.1; Kuklewicz, Jeremi 1; Corey, Robin A.2; Bi, Yunchen 3,9; Ho, Ruoya 1; Mateusiak, Lukasz 4; Pardon, Els 5,6; Steyaert, Jan 5,6; Stansfeld, Phillip J.7,8; Zimmer, Jochen 1
	2022-04-07
发表期刊	NATURE
ISSN	0028-0836
卷号	604 期号:7904 页码:195-+
通讯作者	Zimmer, Jochen(jochen_zimmer@virginia.edu)
摘要	Hyaluronan is an acidic heteropolysaccharide comprising alternating N-acetylglucosamine and glucuronic acid sugars that is ubiquitously expressed in the vertebrate extracellular matrix(1). The high-molecular-mass polymer modulates essential physiological processes in health and disease, including cell differentiation, tissue homeostasis and angiogenesis(2). Hyaluronan is synthesized by a membrane-embedded processive glycosyltransferase, hyaluronan synthase (HAS), which catalyses the synthesis and membrane translocation of hyaluronan from uridine diphosphate-activated precursors(3,4). Here we describe five cryo-electron microscopy structures of a viral HAS homologue at different states during substrate binding and initiation of polymer synthesis. Combined with biochemical analyses and molecular dynamics simulations, our data reveal how HAS selects its substrates, hydrolyses the first substrate to prime the synthesis reaction, opens a hyaluronan-conducting transmembrane channel, ensures alternating substrate polymerization and coordinates hyaluronan inside its transmembrane pore. Our research suggests a detailed model for the formation of an acidic extracellular heteropolysaccharide and provides insights into the biosynthesis of one of the most abundant and essential glycosaminoglycans in the human body.
DOI	10.1038/s41586-022-04534-2
收录类别	SCI
语种	英语
资助项目	Instruct-ERIC, part of the European Strategy Forum on Research Infrastructures (ESFRI) ; Research Foundation-Flanders (FWO) ; NIH[R21AI148853] ; NIH[R01GM101001] ; Wellcome[208361/Z/17/Z] ; BBSRC[BB/P01948X/1] ; BBSRC[BB/R002517/1] ; BBSRC[BB/S003339/1] ; MRC[MR/S009213/1]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000776020400006
出版者	NATURE PORTFOLIO
引用统计	被引频次：38[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/178673
专题	实验海洋生物学重点实验室
通讯作者	Zimmer, Jochen
作者单位	1.Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA 2.Univ Oxford, Dept Biochem, Oxford, England 3.Pilot Natl Lab Marine Sci & Technol Qingdao, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China 4.Vrije Univ Brussel, Lab Vivo Cellular & Mol Imaging, ICMI BEFY, Brussels, Belgium 5.VIB, VIB VUB Ctr Struct Biol, Brussels, Belgium 6.Vrije Univ Brussel, Struct Biol Brussels, Brussels, Belgium 7.Univ Warwick, Sch Life Sci, Coventry, W Midlands, England 8.Univ Warwick, Dept Chem, Coventry, W Midlands, England 9.Chinese Acad Sci, Ctr Ocean Megasci, Inst Oceanol, CAS & Shandong Prov Key Lab Expt Marine Biol, Qingdao, Peoples R China
推荐引用方式 GB/T 7714	Maloney, Finn P.,Kuklewicz, Jeremi,Corey, Robin A.,et al. Structure, substrate recognition and initiation of hyaluronan synthase[J]. NATURE,2022,604(7904):195-+.
APA	Maloney, Finn P..,Kuklewicz, Jeremi.,Corey, Robin A..,Bi, Yunchen.,Ho, Ruoya.,...&Zimmer, Jochen.(2022).Structure, substrate recognition and initiation of hyaluronan synthase.NATURE,604(7904),195-+.
MLA	Maloney, Finn P.,et al."Structure, substrate recognition and initiation of hyaluronan synthase".NATURE 604.7904(2022):195-+.

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