PDBsum entry 2siv

Envelope glycoprotein

PDB id: 2siv

Contents

Protein chains

38 a.a. *

36 a.a. *

Waters ×184

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of the simian immunodeficiency virus (siv) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides.

Authors

V.N.Malashkevich, D.C.Chan, C.T.Chutkowski, P.S.Kim.

Ref.

Proc Natl Acad Sci U S A, 1998, 95, 9134-9139. [DOI no: 10.1073/pnas.95.16.9134]

PubMed id

9689046

Abstract

The gp41 subunit of the envelope protein complex from human and simian immunodeficiency viruses (HIV and SIV) mediates membrane fusion during viral entry. The crystal structure of the HIV-1 gp41 ectodomain core in its proposed fusion-active state is a six-helix bundle. Here we have reconstituted the core of the SIV gp41 ectodomain with two synthetic peptides called SIV N36 and SIV C34, which form a highly helical trimer of heterodimers. The 2.2 A resolution crystal structure of this SIV N36/C34 complex is very similar to the analogous structure in HIV-1 gp41. In both structures, three N36 helices form a central trimeric coiled coil. Three C34 helices pack in an antiparallel orientation into highly conserved, hydrophobic grooves along the surface of this coiled coil. The conserved nature of the N36-C34 interface suggests that the HIV-1 and SIV peptides are functionally interchangeable. Indeed, a heterotypic complex between HIV-1 N36 and SIV C34 peptides is highly helical and stable. Moreover, as with HIV-1 C34, the SIV C34 peptide is a potent inhibitor of HIV-1 infection. These results identify conserved packing interactions between the N and C helices of gp41 and have implications for the development of C peptide analogs with broad inhibitory activity.

Figure 1.
Fig. 1. A schematic view of gp41, showing the locations of the N36 and C34 peptides from SIV and HIV-1. Identical residues between the SIV and HIV-1 peptides are indicated with a bar, and similar residues are indicated by dots. To facilitate comparisons between the HIV-1 and SIV structures, the peptide residues are numbered according to their positions in HIV-1 gp160 (HXB2 strain; GenBank accession no. K03455). For the SIV peptides (SIV Mac239 strain; GenBank accession no. M33262), N36 actually corresponds to positions 559-594, and C34 corresponds to 637-670. The 4,3 hydrophobic repeats are indicated with black shading. FP, fusion peptide; S---S, disulfide bond; TM, transmembrane region; CYTO, cytoplasmic domain.

Figure 5.
Fig. 5. The conserved hydrophobic cavity on the surface of the N36 coiled coil. (A) Structural overlay of the published HIV-1 gp41 ectodomain structures. The three structures [Chan et al. (5), yellow; Weissenhorn et al. (6), red; and Tan et al. (7), green] deviate substantially in this region. (B) Interactions in the N36 hydrophobic cavity of SIV (blue) are most similar to the Chan et al. (5) HIV-1 structure (yellow). The same superposition as in Fig. 4 A and B was used. The SIV N36 coiled coil is represented as a molecular surface, and the C34 helices are shown as ribbons with selected side chains. The molecular surface is colored white for residues that are identical in SIV and HIV, and green for residues that are not identical. Figures were generated with GRASP (28).

Secondary reference #1

Title

Core structure of gp41 from the HIV envelope glycoprotein.

Authors

D.C.Chan, D.Fass, J.M.Berger, P.S.Kim.

Ref.

Cell, 1997, 89, 263-273. [DOI no: 10.1016/S0092-8674(00)80205-6]

PubMed id

9108481

Figure 1.
Fig. 1. A schematic view of gp41, showing the locations

Figure 8.
Figure 8. Comparison of Influenza HA[2], HIV gp41, and Mo-MLV TM StructuresThe top panel shows an end-on view of the three structures from the top, as in the left panel of Figure 3. The bottom panel shows a side view. The three monomers forming the central coiled coil of each structure are colored yellow, green, and blue. Supporting structures are colored purple. Residues 40–129 of HA[2] ([6]) and 45–98 of Mo-MLV TM ( [26]) are included. The figure was generated using the program Insight (Biosym).

The above figures are reproduced from the cited reference with permission from Cell Press