Structure, substrate recognition and initiation of hyaluronan synthase
文献类型：期刊论文
| 作者 | Maloney, Finn P.2; Kuklewicz, Jeremi2; Corey, Robin A.3; Bi, Yunchen1,4; Ho, Ruoya2; Mateusiak, Lukasz5; Pardon, Els6,7; Steyaert, Jan6,7; Stansfeld, Phillip J.8,9; Zimmer, Jochen2 |
| 刊名 | NATURE
 |
| 出版日期 | 2022-04-07 |
| 卷号 | 604期号:7904页码:195-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/s41586-022-04534-2 |
| 通讯作者 | Zimmer, Jochen(jochen_zimmer@virginia.edu) |
| 英文摘要 | 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. |
| 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 |
| 语种 | 英语 |
| WOS记录号 | WOS:000776020400006 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/178672]  |
| 专题 | 海洋研究所_实验海洋生物学重点实验室 |
| 通讯作者 | Zimmer, Jochen |
| 作者单位 | 1.Chinese Acad Sci, Ctr Ocean Megasci, Inst Oceanol, CAS & Shandong Prov Key Lab Expt Marine Biol, Qingdao, Peoples R China 2.Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA 3.Univ Oxford, Dept Biochem, Oxford, England 4.Pilot Natl Lab Marine Sci & Technol Qingdao, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China 5.Vrije Univ Brussel, Lab Vivo Cellular & Mol Imaging, ICMI BEFY, Brussels, Belgium 6.VIB, VIB VUB Ctr Struct Biol, Brussels, Belgium 7.Vrije Univ Brussel, Struct Biol Brussels, Brussels, Belgium 8.Univ Warwick, Sch Life Sci, Coventry, W Midlands, England 9.Univ Warwick, Dept Chem, Coventry, W Midlands, England |
| 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-+. |
入库方式： OAI收割
来源：海洋研究所
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