key: cord-0050919-riqcdg5j
authors: Olson, Norman H.; Kolatkar, Prasanna R.; Oliveira, Marcos A.; Cheng, R. Holland; Greve, Jeffrey M.; McClelland, Alan; Baker, Timothy S.; Rossmann, Michael G.
title: Structure of a human Rhinovirus complexed with its receptor molecule
date: 1993-01-03
journal: Protein Eng
DOI: 10.1093/protein/6.supplement.1
sha: 330f7a3d734f66596f699fdf0c43acb65c29d13f
doc_id: 50919
cord_uid: riqcdg5j

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each pentagonal vertex. Residues lining the canyon are more conserved than other surface residues among rhinovirus serotypes (3). The most variable surface residues are at the sites of attachment of neutralizing antibodies 0,5). It has been proposed that the cellular receptor molecule recognized by the virus binds to conserved residues in the canyon, thus escaping neutralization by host antibodies that are too big to penetrate into that region. This hypothesis 0,6) is supported by site-directed mutagenesis of residues lining the canyon which alters the ability of the virus to attach to HeLa cell membranes (7) . Also, conformational changes in the floor of the canyon, produced by certain antiviral ageflts that bind into a pocket beneath the canyon flooT, inhibit viral attachment to cellular membranes (8) . Conservation of the viral attachment site inside a surface depression has been observed for Mengo (9) and influenza virus (10).

There are well over 100 human rhinovirus serotypes, which can be divided into roughly two groups according to the cellular receptor they recognize 01,12). The structures of human rhinovirus 14 (HRVI4) (1) , which belongs to the major group of serotypes, and of HRVIA (13) Truncated proteins corresponding to the two amino-terminal domains of ICAM-1 (tlCAM-I085)) as well as the intact extracellular portion of ICAM-I (tICAM-1(453) or domains DI to D5) have been expressed in CHO cells (28) . The desialated form of tICAM-I(85), which will be referred to hereafter as molecule DI D2, has recently been crystallized (29) .

Cryoelectron microscopy and image analysis techniques have been used to calculate a three-dimensional reconstruction of the complex of HRV16 and DID2 to -28 A resolution. The reconstruction clearly shows that the receptor binds into the canyon of rhinovirus as predicted 0,5). In addition, we use the known structures of HRV14 and CD4 and the predicted structure of DI ofICAM-l to identify atomic interactions.

Purdue University, West Lafayette

Proc. Natl. Acad. Sci

Proc. Nat!. Acad. Sci