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TitleStructural intermediates in the low pH-induced transition of influenza hemagglutinin.
Journal, issue, pagesPLoS Pathog, Vol. 16, Issue 11, Page e1009062, Year 2020
Publish dateNov 30, 2020
AuthorsJingjing Gao / Miao Gui / Ye Xiang /
PubMed AbstractThe hemagglutinin (HA) glycoproteins of influenza viruses play a key role in binding host cell receptors and in mediating virus-host cell membrane fusion during virus infection. Upon virus entry, HA ...The hemagglutinin (HA) glycoproteins of influenza viruses play a key role in binding host cell receptors and in mediating virus-host cell membrane fusion during virus infection. Upon virus entry, HA is triggered by low pH and undergoes large structural rearrangements from a prefusion state to a postfusion state. While structures of prefusion state and postfusion state of HA have been reported, the intermediate structures remain elusive. Here, we report two distinct low pH intermediate conformations of the influenza virus HA using cryo-electron microscopy (cryo-EM). Our results show that a decrease in pH from 7.8 to 5.2 triggers the release of fusion peptides from the binding pockets and then causes a dramatic conformational change in the central helices, in which the membrane-proximal ends of the central helices unwind to an extended form. Accompanying the conformational changes of the central helices, the stem region of the HA undergoes an anticlockwise rotation of 9.5 degrees and a shift of 15 Å. The HA head, after being stabilized by an antibody, remains unchanged compared to the neutral pH state. Thus, the conformational change of the HA stem region observed in our research is likely to be independent of the HA head. These results provide new insights into the structural transition of HA during virus entry.
External linksPLoS Pathog / PubMed:33253316 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 4.2 Å
Structure data

EMDB-22652, PDB-7k37:
Structure of full-length influenza HA with a head-binding antibody at pH 7.8
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-22653, PDB-7k39:
Structure of full-length influenza HA with a head-binding antibody at pH 5.2, conformation A, neutral pH-like
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-22654, PDB-7k3a:
Structure of full-length influenza HA with a head-binding antibody at pH 5.2, conformation B, fusion peptide release
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-22655, PDB-7k3b:
Structure of full-length influenza HA with a head-binding antibody at pH 5.2, conformation C, central helices splay
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

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

Source
  • Influenza A virus (A/Hong Kong/1/1968(H3N2))
  • influenza a virus (strain a/hong kong/1/1968 h3n2)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / influenza / virus / hemagglutinin / antibody / low pH

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