Influenza hemagglutinin membrane anchor

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

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)10112-10117
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number40
DOIs
StatePublished - Oct 2 2018

Keywords

  • Cryo-EM
  • Hemagglutinin
  • Influenza
  • Membrane fusion
  • Membrane protein

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