High affinity binding between laminin and laminin binding protein of Leishmania is stimulated by zinc and may involve laminin zinc-finger like sequences.

Abstract

In the course of trying to understand the pathogenesis of leishmaniasis in relation to extracellular matrix (ECM) elements, laminin, a major ECM protein, has been found to bind saturably and with high affinity to a 67-kDa cell surface protein of Leishmania donovani. This interaction involves a single class of binding sites, which are ionic in nature, conformation-dependent and possibly involves sulfhydryls. Binding activity was significantly enhanced by Zn2+, an effect possibly mediated through Cys-rich zinc finger-like sequences on laminin. Inhibition studies with monoclonals against polypeptide chains and specific peptides with adhesive properties revealed that the binding site was localized in one of the nested zinc finger consensus sequences of B1 chain containing the specific pentapeptide sequence, YIGSR. Furthermore, incubation of L. donovani promastigotes with C(YIGSR)3-NH2 peptide amide or antibody directed against the 67-kDa laminin-binding protein (LBP) induced tyrosine phosphorylation of proteins with a molecular mass ranging from 115 to 130 kDa. These studies suggest a role for LBP in the interaction of parasites with ECM elements, which may mediate one or more downstream signalling events necessary for establishment of infection.