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Structure paper

TitleInfluenza hemagglutinin membrane anchor.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 40, Page 10112-10117, Year 2018
Publish dateOct 2, 2018
AuthorsDonald 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 /
PubMed AbstractViruses 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 ...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.
External linksProc Natl Acad Sci U S A / PubMed:30224494 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.87 - 4.2 Å
Structure data

0234

6hjn

EMDB-0234, PDB-6hjn:
Structure of Influenza Hemagglutinin ectodomain (A/duck/Alberta/35/76)
Method: EM (single particle) / Resolution: 3.3 Å

0235

6hjp

EMDB-0235, PDB-6hjp:
Structure of Influenza Hemagglutinin ectodomain (A/duck/Alberta/35/76) in complex with FISW84 Fab Fragment
Method: EM (single particle) / Resolution: 3.3 Å

0236

6hjq

EMDB-0236, PDB-6hjq:
Structure of Full-length Influenza Hemagglutinin (A/duck/Alberta/35/76) in complex with FISW84 Fab Fragment
Method: EM (single particle) / Resolution: 4.1 Å

0237

6hjr

EMDB-0237, PDB-6hjr:
Structure of full-length Influenza Hemagglutinin with tilted transmembrane (A/duck/Alberta/35/76[H1N1])
Method: EM (single particle) / Resolution: 4.2 Å

PDB-6hkg:
Structure of FISW84 Fab Fragment
Method: X-RAY DIFFRACTION / Resolution: 1.87 Å

Chemicals

ChemComp-UPL:
UNKNOWN BRANCHED FRAGMENT OF PHOSPHOLIPID

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-SO4:
SULFATE ION / Sulfate

ChemComp-HOH:
WATER / Water

Source
  • influenza a virus (strain a/duck/alberta/35/1976 h1n1)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Influenza virus / Hemagglutinin / Membrane protein / Membrane fusion / IMMUNE SYSTEM

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