5ldn
A viral capsid:antibody complex
Structural highlights
FunctionCAPSH_ADE05 Major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid. Assembled into trimeric units with the help of the chaperone shutoff protein (By similarity). Transported by pre-protein VI to the nucleus where it associates with other structural proteins to form an empty capsid. Might be involved, through its interaction with host dyneins, in the intracellular microtubule-dependent transport of incoming viral capsid to the nucleus. Publication Abstract from PubMedDuring infection with non-enveloped viruses, antibodies stimulate immunity from inside cells by activating the cytosolic Fc receptor TRIM21. This intracellular humoral response relies on opsonized viral particles reaching the cytosol intact but the antigenic and kinetic constraints involved are unknown. We have solved the structure of a potent TRIM21-dependent neutralizing antibody in complex with human adenovirus 5 hexon and show how these properties influence immune activity. Structure-guided mutagenesis was used to generate antibodies with 20,000-fold variation in affinity, on-rates that differ by ~50-fold and off-rates by >175-fold. Characterization of these variants during infection revealed that TRIM21-dependent neutralization and NFkappaB activation was largely unaffected by on-rate kinetics. In contrast, TRIM21 antiviral activity was exquisitely dependent upon off-rate, with sub-muM affinity antibodies nevertheless unable to stimulate signaling because of fast dissociation kinetics. These results define the antibody properties required to elicit an efficient intracellular immune response during viral infection. Antibody-antigen kinetics constrain intracellular humoral immunity.,Bottermann M, Lode HE, Watkinson RE, Foss S, Sandlie I, Andersen JT, James LC Sci Rep. 2016 Nov 24;6:37457. doi: 10.1038/srep37457. PMID:27881870[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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