COMPARATIVE MOLECULAR MODELING OF THE FAS-LIGAND AND OTHER MEMBERS OFTHE TNF FAMILY

A number of proteins with significant similarity to the tumour necrosi s factor (TNF) have been identified over the last years. Upon interact ion with their cognate receptor (members of the TNF-receptor family), all members of this protein family induce either cell death or prolife ration/differentiation of the receptor-bearing cells. One of the last identified members of the TNF family is the apoptosis-inducing ligand of the Fas-receptor, termed Fas-ligand (Fast). Here we report the clon ing and sequencing of the mouse cDNA for the Fast. Using knowledge-bas ed protein modelling, we demonstrate that all members of the TNF famil y form trimeric complexes, and define the residues located at the subu nit interfaces. The resulting structurally corrected multiple sequence alignment allows the identification of residues potentially involved in receptor recognition, and should help design mutagenesis experiment s for structure-function relationship studies.