Determinants of the specificity of rotavirus interactions with the alpha2beta1 integrin.

ABSTRACT: The human ?2?1 integrin binds collagen and acts as a cellular receptor for rotaviruses and human echovirus 1. These ligands require the inserted (I) domain within the ?2 subunit of ?2?1 for binding. Previous studies have identified the binding sites for collagen and echovirus 1 in the ?2 I domain. We used CHO cells expressing mutated ?2?1 to identify amino acids involved in binding to human and animal rotaviruses. Residues where mutation affected rotavirus binding were located in several exposed loops and adjacent regions of the ?2 I domain. Binding by all rotaviruses was eliminated by mutations in the activation-responsive ?C-?6 and ?F helices. This is a novel feature that distinguishes rotavirus from other ?2?1 ligands. Mutation of residues that co-ordinate the metal ion (Ser-153, Thr-221, and Glu-256 in ?2 and Asp-130 in ?1) and nearby amino acids (Ser-154, Gln-215, and Asp-219) also inhibited rotavirus binding. The importance of most of these residues was greatest for binding by human rotaviruses. These mutations inhibit collagen binding to ?2?1 (apart from Glu-256) but do not affect echovirus binding. Overall, residues where mutation affected both rotavirus and collagen recognition are located at one side of the metal ion-dependent adhesion site, whereas those important for collagen alone cluster nearby. Mutations eliminating rotavirus and echovirus binding are distinct, consistent with the respective preference of these viruses for activated or inactive ?2?1. In contrast, rotavirus and collagen utilize activated ?2?1 and show an overlap in ?2?1 residues important for binding.

SUBMITTER: Fleming FE 

PROVIDER: S-EPMC3057834 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature