Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41.
The solution structure of the ectodomain of simian immunodeficiency virus (SIV) gp41 (e-gp41), consisting of residues 27-149, has been determined by multidimensional heteronuclear NMR spectroscopy. SIV e-gp41 is a symmetric 44 kDa trimer with each subunit consisting of antiparallel N-terminal (residues 30-80) and C-terminal (residues 107-147) helices connected by a 26 residue loop (residues 81-106). The N-terminal helices of each subunit form a parallel coiled-coil structure in the interior of the complex which is surrounded by the C-terminal helices located on the exterior of the complex. The loop region is ordered and displays numerous intermolecular and non-sequential intramolecular contacts. The helical core of SIV e-gp41 is similar to recent X-ray structures of truncated constructs of the helical core of HIV-1 e-gp41. The present structure establishes unambiguously the connectivity of the N- and C-terminal helices in the trimer, and characterizes the conformation of the intervening loop, which has been implicated by mutagenesis and 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 represents one of the largest protein structures determined by NMR to date.
Caffrey
M
M
Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
Cai
M
M
Kaufman
J
J
Stahl
S J
SJ
Wingfield
P T
PT
Covell
D G
DG
Gronenborn
A M
AM
Clore
G M
GM
D000595:Amino Acid Sequence; D001665:Binding Sites; D002459:Cell Fusion; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D012191:Retroviridae Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D055672:Static Electricity
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008562:Membrane Glycoproteins; D012191:Retroviridae Proteins; C082614:SIV envelope protein gp41; D012996:Solutions