An aspartate residue of the Yersinia pseudotuberculosis invasin protein that is critical for integrin binding.
The Yersinia pseudotuberculosis invasin protein mediates bacterial entry into mammalian cells by binding multiple beta 1-chain integrins. Invasin binding to purified alpha 5 beta 1 integrin is inhibited by Arg-Gly-Asp (RGD)-containing peptides, although invasin contains no RGD sequence. Fifteen mutations that diminished binding and bacterial entry were isolated after mutagenesis of the entire inv gene. All of the mutations altered residues within the C-terminal 192 amino acids of invasin, previously delineated as the integrin binding domain, and 10 of the mutations fell within an 11 residue region. This small region was subjected to site-directed mutagenesis and almost half of the 35 mutations generated decreased invasin-mediated entry. D911 within this region was the most critical residue, as even a conservative glutamate substitution abolished bacterial penetration. Purified invasin derivatives altered at this residue were defective in promoting cell attachment and this defect was reflected in a 10-fold or greater increase in IC50 for integrin binding. D911 may have a function similar to that of the aspartate residue in RGD-containing sequences.
Leong
J M
JM
Department of Medicine, Tufts-New England Medical Center Hospital, Boston, MA.
Morrissey
P E
PE
Marra
A
A
Isberg
R R
RR
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics; D001422:Bacterial Adhesion / Q000235:genetics*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D004220:Disulfides; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017469:Receptors, Fibronectin; D013329:Structure-Activity Relationship; D014774:Virulence / Q000235:genetics; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000472:pathogenicity*
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D004220:Disulfides; D016023:Integrins; D017469:Receptors, Fibronectin; C053476:invasin, Yersinia; D001224:Aspartic Acid