Homomeric interactions between transmembrane proteins of Moloney murine leukemia virus.

We have studied homomeric interactions between transmembrane proteins (TM) of the Moloney murine leukemiavirusenvelopeusingtheSaccharomycescerevisiaetwo-hybridsystem.TMinteractsstronglywithitself but not with various control proteins. Deletional and mutational analyses indicated that the putative leucine zippermotifintheextracellulardomainofTMisessentialandsufficienttomediatethebinding.Thefirstthree repeats of the leucine zipper-like motif are the most important in mediating the interaction. The TM-TM interaction detected in this system may play a role in several stages of viral replication. Envelope proteins of retroviruses, including those of Moloney murine leukemia virus (Mo-MuLV), are synthesized in infected cells as a glycoprotein precursor (19, 41; for a review, see reference 16). These glycoproteins form oligomers in the lumen of the endoplasmic reticulum and are subsequently cleaved in the Golgi apparatus by host proteases into two subunits: the extracellular surface protein (SU) and the transmembrane protein (TM) which spans the membrane (12, 27). SU and TM remain associated with each other and are anchoredtothemembranethroughTM(32).Thereareprobably multiple contacts in both SU and TM domains responsible for oligomerization (37). Envelope proteins have two major functionsduringviralreplication.First,theymediatebindingofthe