Hydrogen-Deuterium Exchange Supports Independent Membrane-Interfacial Fusion Peptide and Transmembrane Domains in Subunit 2 of Influenza Virus Hemagglutinin Protein, a Structured and Aqueous-Protected Connection between the Fusion Peptide and Soluble Ectodomain, and the Importance of Membrane Apposition by the Trimer-of-Hairpins Structure.

ABSTRACT: The influenza virus hemagglutinin (HA) protein has HA1 and HA2 subunits, which form an initial complex. HA1's bind host cell sialic acids, which triggers endocytosis, HA1/HA2 separation, and HA2-mediated fusion between virus and endosome membranes. We report hydrogen-deuterium exchange mass spectrometry (HDX-MS) on the HA2 subunit without HA1. HA2 contains the fusion peptide (FP), soluble ectodomain (SE), transmembrane domain (TM), and endodomain. FP is a monomer by itself, while SE is a trimer of hairpins that includes an interior bundle of residue 38-105 helices, turns, and residue 154-178 strands packed antiparallel to the bundle. FP and TM extend from the same side of the SE hairpin, and fusion models often depict a FP/TM complex with membrane traversal of both domains that is importan

SUBMITTER: Ranaweera A 

PROVIDER: S-EPMC6536117 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature