Integrin beta1-chain residues involved in substrate recognition and specificity of binding to invasin.
A highly conserved 14-amino-acid region of the chicken beta1 integrin chain (beta1chk residues 151-168) hypothesized to be involved in divalent cation coordination was analysed to determine whether invasin uses the same structural determinants as fibronectin (Fn) to recognize receptors. For the most part, both proteins required similar beta1 chain residues for integrin recognition, although the relative preference of the integrin for the two substrates could be inverted mutationally. Substitution mutations in the amino terminal residues of this region resulted in defective binding to both substrates by the receptor, while substitutions at the carboxyl-terminal end of this region were better tolerated. A derivative carrying the double substitution (KDD160RDV) had the unique phenotype of maintaining Fn binding while abolishing invasin binding, indicating that this region of the receptor may determine substrate specificity. These data indicate that the integrin beta1 chain possesses a ligand binding site shared by invasin and Fn that can be altered by mutation to allow greater preference for the normally lower affinity substrate Fn than for invasin. It was also established that the region analysed has the ability to bind divalent cations.
Krukonis
E S
ES
Tufts University School of Medicine, Department of Molecular Biology and Microbiology, Boston, MA 02111, USA.
Isberg
R R
RR
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002645:Chickens; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D058619:Maltose-Binding Proteins; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002413:Cations, Divalent; D005353:Fibronectins; D019012:Integrin beta1; D058619:Maltose-Binding Proteins; D011993:Recombinant Fusion Proteins; C053476:invasin, Yersinia