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Influenza hemagglutinin membrane anchor

DOI: 10.1073/pnas.1810927115 DOI Help

Authors: Donald J. Benton (Francis Crick Institute) , Andrea Nans (Francis Crick Institute) , Lesley J. Calder (Francis Crick Institute) , Jack Turner (Francis Crick Institute) , Ursula Neu (Francis Crick Institute) , Yi Pu Lin (Francis Crick Institute) , Esther Ketelaars (Institute for Research in Biomedicine) , Nicole L. Kallewaard (MedImmune LLC) , Davide Corti (Humabs BioMed) , Antonio Lanzavecchia (Institute for Research in Biomedicine) , Steven Gamblin (Francis Crick Institute) , Peter B. Rosenthal (Francis Crick Institute) , John J. Skehel (Francis Crick Institute)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 115 , PAGES 10112 - 10117

State: Published (Approved)
Published: October 2018
Diamond Proposal Number(s): 9826

Open Access Open Access

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.

Journal Keywords: influenza; hemagglutinin; cryo-EM; membrane protein; membrane fusion

Diamond Keywords: Viruses; Influenza

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography

Added On: 11/10/2018 10:52


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)