A novel integrin specificity exemplified by binding of the alpha v beta 5 integrin to the basic domain of the HIV Tat protein and vitronectin.
Several studies have addressed the interaction of the HIV Tat protein with the cell surface. Our analysis of the cell attachment-promoting activity of Tat and peptides derived from it revealed that the basic domain of Tat, not the arg-gly-asp (RGD) sequence, is required for cell attachment to Tat. Affinity chromatography with Tat peptides and immunoprecipitation with various anti-integrin antibodies suggest that the vitronectin-binding integrin, alpha v beta 5, is the cell surface protein that binds to the basic domain of Tat. The Tat basic domain contains the sequence RKKRRQRRR. A related sequence, KKQRFRHRNRKG, present in the heparin-binding domain of an alpha v beta 5 ligand, vitronectin, also bound alpha v beta 5 in affinity chromatography and, in combination with an RGD peptide, was an inhibitor of cell attachment to vitronectin. The alpha v beta 5 interaction with these peptides was not solely due to high content of basic amino acids in the ligand sequences; alpha v beta 5 did not bind substantially to peptides consisting entirely of arginine or lysine, whereas a beta 1 integrin did bind to these peptides. The interaction of alpha v beta 5 with Tat is atypical for integrins in that the binding to Tat is divalent cation independent, whereas the binding of the same integrin to an RGD-containing peptide or to vitronectin requires divalent cations. These data define an auxiliary integrin binding specificity for basic amino acid sequences. These basic domain binding sites may function synergistically with the binding sites that recognize RGD or equivalent sequences.
Vogel
B E
BE
La Jolla Cancer Research Foundation, California 92037.
Lee
S J
SJ
Hildebrand
A
A
Craig
W
W
Pierschbacher
M D
MD
Wong-Staal
F
F
Ruoslahti
E
E
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent / Q000494:pharmacology; D002460:Cell Line; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006678:HIV / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D019030:Receptors, Vitronectin; D019096:Vitronectin; D054322:tat Gene Products, Human Immunodeficiency Virus
D002413:Cations, Divalent; D015696:Gene Products, tat; D006023:Glycoproteins; D016023:Integrins; D010455:Peptides; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; D054322:tat Gene Products, Human Immunodeficiency Virus