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J Phys Chem B. 2019 Sep 12;123(36):7700-7710. doi: 10.1021/acs.jpcb.9b06430. Epub 2019 Aug 27.

Structure of the Functionally Important Extracellular Loop C of Human Aquaporin 1 Obtained by Solid-State NMR under Nearly Physiological Conditions.

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1
Department of Physics and Biophysics Interdepartmental Group , University of Guelph , 50 Stone Road E , Guelph , Ontario N1G 2W1 , Canada.

Abstract

Human aquaporin 1 (hAQP1) is the first discovered selective water channel present in lipid membranes of multiple types of cells. Several structures of hAQP1 and its bovine homolog have been obtained by electron microscopy and X-ray crystallography, giving a consistent picture of the transmembrane domain with the water-conducting pore. The transmembrane domain is formed by six full helices and two half-helices, which form a central constriction with conserved asparagine-proline-alanine motifs. Another constriction, the aromatic/arginine (ar/R) filter, is found close to the extracellular surface, and includes aromatic residues and a conserved arginine (Arg-195). Although the existing crystal structures largely converge on the location of helical segments, they differ in details of conformation of the longest extracellular loop C and its interactions with the ar/R filter (in particular, with Arg-195). Here, we use solid-state nuclear magnetic resonance to determine multiple interatomic distances, and come up with a refined structural model for hAQP1, which represents a physiologically relevant state predominant at noncryogenic temperatures in a lipid environment. The model clearly disambiguates the position of the Arg-195 sidechain disputed previously and shows a number of interactions for loop C, both with the ar/R filter and a number of other residues on the extracellular side of hAQP1.

PMID:
31411472
DOI:
10.1021/acs.jpcb.9b06430

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