VARIANT-SPECIFIC SURFACE-PROTEINS OF GIARDIA-LAMBLIA ARE ZINC-BINDINGPROTEINS

Giardia lamblia undergoes surface antigenic variation. The variant-spe cific surface proteins (VSPs) are a distinct family of cysteine-rich p roteins. Characteristically, cysteine residues occur mostly as CXXC te trapeptides. Four of the reported five VSPs contain a putative metal-b inding domain that resembles other metal-binding motifs; the fifth is closely related but lacks an essential histidine. Three different nati ve VSPs bound Zn2+. Co2+, Cu2+, and Cd2+ inhibited Zn2+ binding. Analy sis of recombinant VSP fusion proteins showed that the putative bindin g motif bound Zn2+. Surprisingly, peptide fragments from other regions of the VSP contain numerous CXXCX(n)CXXC motifs that also bound Zn2+. Analysis of deduced amino acid sequences showed well-conserved CXXC s pacing in three out of rive VSPs, suggesting conservation of structure despite amino acid sequence divergence. The function of VSPs is unkno wn, but by binding Zn2+ or other metals in the intestine, VSPs may con tribute to Zn2+ malnutrition or inhibition of metal-dependent intestin al enzymes, which would lead to malabsorption, a well-known consequenc e of giardiasis.