Variant-specific surface proteins of Giardia lamblia are zinc-binding proteins.

Giardia lamblia undergoes surface antigenic variation. The variant-specificsurface proteins (VSPs) are a distinct family of cysteine-rich proteins. Characteristically, cysteineresidues occur mostly as CXXC tetrapeptides. Four of the reported five VSPs contain a putative metal-bindingdomain that resembles other metal-binding motifs; the fifth is closely related but lacks an essentialhistidine. Three different native VSPs bound Zn2+. Co2+, Cu2+, and Cd2+ inhibited Zn2+ binding. Analysisof recombinant VSP fusion proteins showed that the putative binding motif bound Zn2+. Surprisingly, peptidefragments from other regions of the VSP contain numerous CXXCXnCXXC motifs that also bound Zn2+. Analysisof deduced amino acid sequences showed well-conserved CXXC spacing in three out of five VSPs, suggestingconservation of structure despite amino acid sequence divergence. The function of VSPs is unknown, butby binding Zn2+ or other metals in the intestine, VSPs may contribute to Zn2+ malnutrition or inhibitionof metal-dependent intestinal enzymes, which would lead to malabsorption, a well-known consequence ofgiardiasis.