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Full-length, Oligomeric Structure of Wzz Determined by Cryoelectron Microscopy Reveals Insights into Membrane-Bound States
Wzz is an integral inner membrane protein involved in regulating the length of lipopolysaccharide O-antigen glycans and essential for the virulence of many Gram-negative pathogens. In all Wzz homologs, the large periplasmic domain is proposed to be anchored by two transmembrane helices, but no infor...
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Published in: | Structure (London) 2017-05, Vol.25 (5), p.806-815.e3 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Wzz is an integral inner membrane protein involved in regulating the length of lipopolysaccharide O-antigen glycans and essential for the virulence of many Gram-negative pathogens. In all Wzz homologs, the large periplasmic domain is proposed to be anchored by two transmembrane helices, but no information is available for the transmembrane and cytosolic domains. Here we have studied purified oligomeric Wzz complexes using cryoelectron microscopy and resolved the transmembrane regions within a semi-continuous detergent micelle. The transmembrane helices of each monomer display a right-handed super-helical twist, and do not interact with the neighboring transmembrane domains. Modeling, flexible fitting and multiscale simulation approaches were used to study the full-length complex and to provide explanations for the influence of the lipid bilayer on its oligomeric status. Based on structural and in silico observations, we propose a new mechanism for O-antigen chain-length regulation that invokes synergy of Wzz and its polymerase partner, Wzy.
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•Wzz regulates chain length of lipopolysaccharide O-antigen in pathogenic bacteria•Full-length, oligomeric structure of Wzz determined by cryoelectron microscopy•Integrative modeling and multiscale simulations yield membrane-bound states•Mechanistic model for Wzz proposed, invokes synergy with polymerase partner Wzy
Control of lipopolysaccharide O-antigen chain length is essential in the virulence of bacterial pathogenesis, and is regulated by the Wzz protein. Collins et al. use a combination of experimental and computational approaches to resolve the membrane domains of Wzz and provide clues to its mechanism of action. |
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ISSN: | 0969-2126 1878-4186 |
DOI: | 10.1016/j.str.2017.03.017 |