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Publication Abstract from PubMed

The coxsackievirus and adenovirus receptor (CAR) has been identified as the cellular receptor for group B coxsackieviruses, including serotype 3 (CVB3). CAR mediates infection by binding to CVB3 and catalyzing conformational changes in the virus that result in formation of the altered, non-infectious "A-particle". Kinetic analyses show that the apparent first-order rate constant for the inactivation of CVB3 by soluble CAR (sCAR) at physiological temperatures varies non-linearly with sCAR concentration. The cryo-electron microscopy (cryo-EM) reconstruction of the CVB3-CAR complex resulted in a 9.0 A resolution map that was interpreted with the four available crystal structures of CAR, providing a consensus footprint for the receptor-binding site. The analysis of the cryo-EM structure identifies important virus-receptor interactions that are conserved across picornavirus species. These conserved interactions map to variable antigenic sites or structurally conserved regions, suggesting a combination of evolutionary mechanisms for receptor site preservation. The CAR-catalyzed A-particle structure was solved to 6.6 A resolution and shows significant rearrangement of internal features and symmetric interactions with the RNA genome. STATEMENT OF IMPORTANCE: Our manuscript presents new information about receptor use by picornaviruses and highlights the importance of attaining at least approximately 9 A resolution for the interpretation of cryoEM complex maps. The analysis of receptor binding elucidates two complementary mechanisms for preservation of the low affinity (initial) interaction of receptor and defines the kinetics of receptor catalyzed conformational change to the A-particle.

Kinetic and structural analysis of coxsackievirus B3 receptor interactions and formation of the A-particle.,Organtini LJ, Makhov AM, Conway JF, Hafenstein S, Carson SD J Virol. 2014 Mar 12. PMID:24623425^[1]

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