Cited by 45Receptor Mechanisms and SignalingProtein Structure and DynamicsEnzyme Structure and Function

Visualizing Water Molecules in Transmembrane Proteins Using Radiolytic Labeling Methods

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Orban, Tivadar, Gupta, Sayan, Palczewski, Krzysztof, Chance, Mark R.·2010·Biochemistry

Abstract

Essential to cells and their organelles, water is both shuttled to where it is needed and trapped within cellular compartments and structures. Moreover, ordered waters within protein structures often colocalize with strategically placed polar or charged groups critical for protein function, yet it is unclear if these ordered water molecules provide structural stabilization, mediate conformational changes in signaling, neutralize charged residues, or carry out a combination of all these functions. Structures of many integral membrane proteins, including G protein-coupled receptors (GPCRs), reveal the presence of ordered water molecules that may act like prosthetic groups in a manner quite unlike bulk water. Identification of "ordered" waters within a crystalline protein structure requires sufficient occupancy of water to enable its detection in the protein's X-ray diffraction pattern, and thus, the observed waters likely represent a subset of tightly bound functional waters. In this review, we highlight recent studies that suggest the structures of ordered waters within GPCRs are as conserved (and thus as important) as conserved side chains. In addition, methods of radiolysis, coupled to structural mass spectrometry (protein footprinting), reveal dynamic changes in water structure that mediate transmembrane signaling. The idea of water as a prosthetic group mediating chemical reaction dynamics is not new in fields such as catalysis. However, the concept of water as a mediator of conformational dynamics in signaling is just emerging, because of advances in both crystallographic structure determination and new methods of protein footprinting. Although oil and water do not mix, understanding the roles of water is essential to understanding the function of membrane proteins.

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  • Rhodopsin activation involves geometric cis/trans isomerization of the chromophore, deprotonation of the Schiff linkage, and reorganization of water molecules within the transmembrane domain.

    “This activation is accomplished through geometric cis/trans isomerization of the chromophore,182 deprotonation of the Schiff linkage,339 and reorganization of water molecules within the TMD of this receptor.”

    From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [342]

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Research works printed but not linked: 2

  1. [16]Chance MR 2008 Mass Spectrometry Analysis for Protein Interactions and Dynamics Wiley-Blackwell
  2. [79]Gupta S Bravo V Tucker S Venien-Bryan C Chance MR 2010 Probing the structure of an ion channel by structural mass spectrometry Biophysical J in press

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Authors
Orban, T., Gupta, S., Palczewski, K., & Chance, M. R.
Affiliations
  • Case Western Reserve University (US)
  • Center for Proteomics and Bioinformatics
  • Department of Pharmacology
Corresponding author
  • Palczewski, Krzysztof
  • Chance, Mark R.
Venue
Biochemistry
Published
2010-01-11
Volume
49
Issue
5
Pages
827-834
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2132251312
Cited by
45
References
89
Citations by year
2026: 1 · 2023: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 5 · 2012: 6
FWCI
0.67
Type
journal article
Language
en
Open access
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Eye Institute (K99EY018085, R00EY018085, EY009339, EY018085, R01EY009339)
  • National Institute of General Medical Sciences (GM 079191, R01GM079191)
  • National Institute of Biomedical Imaging and Bioengineering (EB09688, EB09998, R01EB009688, P30EB009998, P41EB001979)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
ordered water molecules, transmembrane proteins, G protein-coupled receptors, radiolysis, protein footprinting, conformational dynamics, transmembrane signaling, integral membrane proteins
MeSH terms
Animals, Humans, Membrane Proteins, Magnetic Resonance Spectroscopy, Rhodopsin, Water, Hydroxyl Radical, Crystallography, X-Ray, Protein Footprinting, Receptors, G-Protein-Coupled

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