Structural and functional definition of a vulnerable site on the hemagglutinin of highly pathogenic avian influenza A virus H5N1 [Protein Structure and Folding]

In this study, we report the crystal structures of two additional human H5N1 antibodies isolated from H5N1-infected individuals, 3C11 and AVFluIgG01, bound to the head at 2.33- and 2.30-Å resolution, respectively. These two new antibody epitopes have large overlap with and extend beyond the original VS1. Site-directed mutagenesis experiments identified eight pivotal residues (Ser-126b, Lys-165, Arg-166, Ser-167, Tyr-168, Asn-169, Thr-171, and Asn-172) critical for 65C6-, 3C11-, and AVFluIgG01-binding and neutralization activities. These residues formed a unique “Y”-shaped surface on H5N1 globular head and are highly conserved among H5N1 viruses. Our results further support the existence of a vulnerable site distinct from the RBS and the stem region of H5N1 HA, and future design of immunogens should take this particular site into consideration.

Source: Journal of Biological Chemistry - March 21, 2019 Category: Chemistry Authors: Pengfei Wang, Yanan Zuo, Jianfeng Sun, Teng Zuo, Senyan Zhang, Shichun Guo, Xuanling Shi, Mifang Liang, Paul Zhou, Linqi Zhang, Xinquan Wang Tags: Editors ' Picks Source Type: research