We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

9azt

From Proteopedia

Jump to: navigation, search

CH67 Fab bound to A/Massachusetts/1/1990 influenza hemagglutinin head with a G189E mutation (1)

Structural highlights

9azt is a 3 chain structure with sequence from Homo sapiens and Influenza A virus (A/Massachusetts/1/1990(H1N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.94Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q07775_9INFA Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[RuleBase:RU003324]

Publication Abstract from PubMed

Initial exposure to a rapidly evolving virus establishes B cell memory that biases later responses to antigenically drifted strains. This "immune imprinting" implies that subsequent exposure to a drifted strain can induce affinity maturation of memory B cells toward cross-reactivity with the drifted strain and hence toward greater overall breadth. Here, we used deep mutational scanning of H1 influenza hemagglutinins (HAs) to investigate how viruses evolve in response to these broad antibody response. We identified escape mutations from clonal antibody lineages that targeted the receptor binding site and lateral patch. By adjusting the antigen-antibody contacts, antibody affinity maturation restricted the potential escape routes for the eliciting strain. However, escape occurred readily in drifted strains. We attribute this escape-prone property of the drifted strains to epistatic networks within HA. Our data explain how the influenza virus continues to evolve in the human population by escaping even broad antibody responses.

Antigenic drift expands influenza viral escape pathways from recalled humoral immunity.,Maurer DP, Vu M, Schmidt AG Immunity. 2025 Feb 25:S1074-7613(25)00074-3. doi: 10.1016/j.immuni.2025.02.006. PMID:40023162^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Maurer DP, Vu M, Schmidt AG. Antigenic drift expands influenza viral escape pathways from recalled humoral immunity. Immunity. 2025 Feb 25:S1074-7613(25)00074-3. PMID:40023162 doi:10.1016/j.immuni.2025.02.006