Abstract
Hemagglutinin (HA) is a class I viral membrane fusion protein, which is the most abundant transmembrane protein on the surface of influenza A virus (IAV) particles. HA plays a crucial role in the recognition of the host cell, fusion of the viral envelope and the host cell membrane, and is the major antigen in the immune response during the infection. Mature HA organizes in homotrimers consisting of a sequentially highly variable globular head and a relatively conserved stalk region. Every HA monomer comprises a hydrophilic ectodomain, a pre-transmembrane domain (pre-TMD), a hydrophobic transmembrane domain (TMD), and a cytoplasmic tail (CT). In recent years the effect of the pre-TMD and TMD on the structure and function of HA has drawn some attention. Using bioinformatic tools we analyzed all available full-length amino acid sequences of HA from 16 subtypes across various host species. We calculated several physico-chemical parameters of HA pre-TMDs and TMDs including accessible surface area (ASA), average hydrophobicity (H(av)), and the hydrophobic moment (µ(H)). Our data suggests that distinct differences in these parameters between the two major phylogenetic groups, represented by H1 and H3 subtypes, could have profound effects on protein-lipid interactions, trimer formation, and the overall HA ectodomain orientation and antigen exposure.