6hcn | pdb_00006hcn
Adenovirus Type 5 Fiber Knob protein at 1.49A resolution
Structural highlights
Function[SPIKE_ADE05] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host coxsackievirus and adenovirus receptor CXADR located at the cell tight junctions to provide virion initial attachment to target cell. The fiber protein binds to CXADR with a higher affinity than CXADR binds to itself, thereby blocking the cell-cell adhesion function of CXADR dimers and leading to local disruption of the tight junction. Fiber protein present on neo-synthesized particles may thus disrupt the junctional integrity in order to facilitate further neighboring cells infection. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Fiber shedding is dependent on viral CXADR drifting motion and subsequent binding to immobile integrins. Heparan sulfate might also play a role in virus binding (By similarity). Publication Abstract from PubMedAdenovirus based vectors are of increasing importance for wide ranging therapeutic applications. As vaccines, vectors derived from human adenovirus species D serotypes 26 and 48 (HAdV-D26/48) are demonstrating promising efficacy as protective platforms against infectious diseases. Significant clinical progress has been made, yet definitive studies underpinning mechanisms of entry, infection, and receptor usage are currently lacking. Here, we perform structural and biological analysis of the receptor binding fiber-knob protein of HAdV-D26/48, reporting crystal structures, and modelling putative interactions with two previously suggested attachment receptors, CD46 and Coxsackie and Adenovirus Receptor (CAR). We provide evidence of a low affinity interaction with CAR, with modelling suggesting affinity is attenuated through extended, semi-flexible loop structures, providing steric hindrance. Conversely, in silico and in vitro experiments are unable to provide evidence of interaction between HAdV-D26/48 fiber-knob with CD46, or with Desmoglein 2. Our findings provide insight into the cell-virus interactions of HAdV-D26/48, with important implications for the design and engineering of optimised Ad-based therapeutics. Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions.,Baker AT, Greenshields-Watson A, Coughlan L, Davies JA, Uusi-Kerttula H, Cole DK, Rizkallah PJ, Parker AL Nat Commun. 2019 Feb 14;10(1):741. doi: 10.1038/s41467-019-08599-y. PMID:30765704[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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