Structure and Dynamics of Extracellular Loops in Human Aquaporin-1 from   Solid-State NMR and Molecular Dynamics

doi:10.1021/acs.jpcb.6b06731

CORC > 北京大学 > 化学与分子工程学院

	Structure and Dynamics of Extracellular Loops in Human Aquaporin-1 from Solid-State NMR and Molecular Dynamics
	Wang, Shenlin ; Ing, Christopher ; Emami, Sanaz ; Jiang, Yunjiang ; Liang, Hongjun ; Pomes, Regis ; Brown, Leonid S. ; Ladizhansky, Vladimir
刊名	JOURNAL OF PHYSICAL CHEMISTRY B
	2016
关键词	HYDROGEN-DEUTERIUM EXCHANGE PROTEIN SECONDARY STRUCTURE HUMAN MEMBRANE-PROTEIN ANGLE-SPINNING NMR WATER PERMEATION FORCE-FIELD CHANNELS SPECTROSCOPY SIMULATIONS TRANSPORT
DOI	10.1021/acs.jpcb.6b06731
英文摘要	Multiple moderate-resolution crystal structures of human aquaporin-1 have provided a foundation for understanding the molecular mechanism of selective water translocation in human cells. To gain insight into the interfacial structure and dynamics of human aquaporin-1 in a lipid environment, we performed nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations. Using magic angle spinning solid-state NMR, we report a near complete resonance assignment of the human aquaporin-1. Chemical shift analysis of the secondary structure identified pronounced deviations from crystallographic structures in extracellular loops A and C, including the cis Y37-P38 bond in loop A, as well as ordering and immobilization of loop C. Site-specific H/D exchange measurements identify a number of protected nitrogen-bearing side chains and backbone amide groups, involved in stabilizing the loops. A combination of molecular dynamics simulations with NMR-derived restraints and filtering based on solvent accessibility allowed for the determination of a structural model of extracellular loops largely consistent with NMR results. The simulations reveal loop stabilizing interactions that alter the extracellular surface of human AQP1, with possible implications for water transport regulation through the channel. Modulation of water permeation may occur as a result of rearrangement of side chains from loop C in the extracellular vestibule of hAQP1, affecting the aromatic arginine selectivity filter.; NSERC [RGPIN-2014-04.547, RGPIN-2013-250202]; NSF-DMR [1623241]; NSF-CBET [1623240]; CIHR [MOP-130461]; Canada Foundation for Innovation under Compute Canada; Government of Ontario, Ontario Research Fund - Research Excellence; University of Toronto; U.S. Department of Energy, Office of Basic Energy Sciences [DE-AC02-765F00515]; CIHR; Ontario Trillium Scholarship; SCI(E); EI; ARTICLE; lebrown@uoguelph.ca; vladizha@uoguelph.ca; 37; 9887-9902; 120
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/450027]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Wang, Shenlin,Ing, Christopher,Emami, Sanaz,et al. Structure and Dynamics of Extracellular Loops in Human Aquaporin-1 from Solid-State NMR and Molecular Dynamics[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2016.
APA	Wang, Shenlin.,Ing, Christopher.,Emami, Sanaz.,Jiang, Yunjiang.,Liang, Hongjun.,...&Ladizhansky, Vladimir.(2016).Structure and Dynamics of Extracellular Loops in Human Aquaporin-1 from Solid-State NMR and Molecular Dynamics.JOURNAL OF PHYSICAL CHEMISTRY B.
MLA	Wang, Shenlin,et al."Structure and Dynamics of Extracellular Loops in Human Aquaporin-1 from Solid-State NMR and Molecular Dynamics".JOURNAL OF PHYSICAL CHEMISTRY B (2016).