3-DIMENSIONAL SOLUTION STRUCTURE OF THE 44 KDA ECTODOMAIN OF SIV GP41

The solution structure of the ectodomain of simian immunodeficiency vi rus (SIV) gp41 (e-gp41), consisting of residues 27-149, has been deter mined by multidimensional heteronuclear NMR spectroscopy. SN e-gp41 is a symmetric 44 kDa trimer with each subunit consisting of antiparalle l N-terminal (residues 30-80) and C-terminal (residues 107-147) helice s connected by a 26 residue loop (residues 81-106), The N-terminal hel ices of each subunit form a parallel coiled-coil structure in the inte rior of the complex which is surrounded by the C-terminal helices loca ted on the exterior of the complex, The loop region is ordered and dis plays numerous intermolecular and non-sequential intramolecular contac ts. The helical core of SIV e-gp41 is similar to recent X-ray structur es of truncated constructs of the helical core of HIV-1 e-gp41. The pr esent structure establishes unambiguously the connectivity of the N- a nd C-terminal helices in the trimer, and characterizes the conformatio n of the intervening loop, which has been implicated by mutagenesis an d antibody epitope mapping to play a key role in gp120 association, In conjunction with previous studies, the solution structure of the SIV e-gp41 ectodomain provides insight into the binding site of gp120 and the mechanism of cell fusion. The present structure of SIV e-gp41 repr esents one of the largest protein structures determined by NMR to date .