Influenza hemagglutinin membrane anchor

Benton, Donald J.; Nans, Andrea; Calder, Lesley J.; Turner, Jack; Neu, Ursula; Lin, Yi Pu; Ketelaars, Esther; Kallewaard, Nicole L.; Corti, Davide; Lanzavecchia, Antonio; Gamblin, Steven J.; Rosenthal, Peter B.; Skehel, John J.

doi:10.1073/pnas.1810927115

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Journal article

Influenza hemagglutinin membrane anchor

Università della Svizzera italiana

Benton, Donald J. Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom
Nans, Andrea Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom - Structural Biology Science Technology Platform, Francis Crick Institute, NW1 1AT London, United Kingdom
Calder, Lesley J. Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom
Turner, Jack Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom
Neu, Ursula Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom
Lin, Yi Pu Worldwide Influenza Centre, Francis Crick Institute, NW1 1AT London, United Kingdom
Ketelaars, Esther Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Kallewaard, Nicole L. MedImmune LLC, Gaithersburg, MD 20878
Corti, Davide Humabs BioMed SA, 6500 Bellinzona, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Gamblin, Steven J. Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom
Rosenthal, Peter B. Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom
Skehel, John J. Structural Biology of Disease Processes Laboratory, Francis Crick Institute, NW1 1AT London, United Kingdom

17.09.2018

Published in:

Proceedings of the national academy of sciences of the United States of America. - 2018, vol. 115, no. 40, p. 10112-10117

English Viruses with membranes fuse them with cellular membranes, to transfer their genomes into cells at the beginning of infection. For Influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D structure of which is known from X-ray crystallographic studies. The soluble ectodomain fragments used in these studies lacked the “membrane anchor” portion of the molecule. Since this region has a role in membrane fusion, we have determined its structure by analyzing the intact, full-length molecule in a detergent micelle, using cryo-EM. We have also compared the structures of full-length HA−detergent micelles with full-length HA−Fab complex detergent micelles, to describe an infectivity-neutralizing monoclonal Fab that binds near the ectodomain membrane anchor junction. We determine a high- resolution HA structure which compares favorably in detail with the structure of the ectodomain seen by X-ray crystallography; we detect, clearly, all five carbohydrate side chains of HA; and we find that the ectodomain is joined to the membrane anchor by flexible, eight-residue-long, linkers. The linkers extend into the detergent micelle to join a central triple-helical structure that is a major component of the membrane anchor.

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