Gary Davis

The major human rhinovirus receptor is ICAM-1

The major human rhinovirus receptor has been identified with monoclonal antibodies that inhibit rhinovirus infection. These monoclonal antibodies recognize a 95 kd cell surface glycoprotein on human cells and on mouse transfectants expressing a rhinovirus binding phenotype. Purified 95 kd protein binds to rhinovirus in vitro. Protein sequence from the 95 kd protein showed an identity with that of intercellular adhesion molecule-1 (ICAM-1); a cDNA clone obtained from mouse transfectants expressing the rhinovirus receptor had essentially the same sequence as ICAM-1. Thus, the major human rhinovirus receptor is ICAM-1. The gene for this receptor maps to human chromosome 19, which also contains the genes for a number of other picornavirus receptors.

Enhancement of CD2-mediated T cell activation by the interaction of VLA-4 with fibronectin.

Human fibroblasts were shown to enhance the proliferation of peripheral T cells in the presence of suboptimal concentrations of anti-CD2 antibodies (anti-T112 and anti-T113) and agonistic anti-VLA-4 antibody. Evidence is provided that the interaction of VLA-4 with immobilized fibronectin can enhance the proliferation of T cells subjected to suboptimal stimulation via CD2. Our results suggest that the fibroblast-stimulated T cell proliferative response to low doses of anti-T112 and T113 antibodies is due to the interaction of VLA-4 with fibroblast fibronectin. These findings also suggest a role for the fibronectin/VLA-4 interaction in the inflammatory process.

Protein-Protein Interactions in the P450 Monooxygenase System

Cytochrome bs is a small acidic hemoprotein that functions as an electron transfer protein. It is a ubiquitous mammalian membrane protein, found in the endoplasmic reticulum of most tissues. Its primary structure is highly conserved with sequence identities of greater than 89% in mammals and greater than 71% between rat and chicken (Figure I). Even in comparisons between plant (rice and tobacco) cytochrome bs with that of mammals sequence identity is greater than 35%. Twenty-five of the one hundred and thirtythree amino acids of rabbit cytochrome bs are acidic residues, glutamate or aspartate. Cytochrome bs has a number of its very highly conserved acidic residues around an exposed heme edge (Figure 2), some of which are delineated in Figure I (bold type). Residues around the exposed heme and the heme are shown in ball and stick model. It was shown quite early that cytochrome bs uses its acidic residues for stabilization of interactions with its electron transfer (redox) partners. Although not its normal redox partner, cytochrome c has been used to study electron transfer with cytochrome b5, and, since the crystal structure of both proteins have been elucidated,I-3 surface maps of the topologies of cytochrome bs and cytochrome c were constructed and fitted together making use of the invariant anionic and cationic charges respectively, ringing the exposed heme prosthetic groups as a means for determining the docking domains of the two proteins. 3 Interaction models between cytochrome b5 and methemoglobin have likewise been constructed which make use of charge pairings. 4 Interaction between erythrocyte cytochrome bs and its reductase was greatly inhibited by increased ionic strength,S which suggested that such interaction also utilizes complementary charge pairing for efficient electron transfer.