Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance

Joseph D. Ho, Ronald Yeh, Andrew Sandstrom, Ilya Chorny, William E.C. Harries, Rebecca A. Robbins, Larry J.W. Miercke, Robert M. Stroud

Research output: Contribution to journalArticlepeer-review

Abstract

Aquaporin (AQP) 4 is the predominant water channel in the mammalian brain, abundantly expressed in the blood-brain and brain- cerebrospinal fluid interfaces of glial cells. Its function in cerebral water balance has implications in neuropathological disorders, including brain edema, stroke, and head injuries. The 1.8-Å crystal structure reveals the molecular basis for the water selectivity of the channel. Unlike the case in the structures of water-selective AQPs AqpZ and AQP1, the asparagines of the 2 Asn-Pro-Ala motifs do not hydrogen bond to the same water molecule; instead, they bond to 2 different water molecules in the center of the channel. Molecular dynamics simulations were performed to ask how this observation bears on the proposed mechanisms for how AQPs remain totally insulating to any proton conductance while maintaining a single file of hydrogen bonded water molecules throughout the channel.

Original languageEnglish (US)
Pages (from-to)7437-7442
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number18
DOIs
StatePublished - May 5 2009
Externally publishedYes

Keywords

  • Brain edema
  • Inhibitor discovery
  • NPA motif

ASJC Scopus subject areas

  • General

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