PDBsum entry: 1meq

Viral protein

PDB id: 1meq

Contents

Protein chain

23 a.a.

PDB id:

1meq

Name:

Viral protein

Title:

HIV gp120 c5

Structure:

Exterior membrane glycoprotein (gp120). Chain: a. Fragment: residues (484-506). Engineered: yes

Source:

Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in human immunodeficiency virus type 1 (HIV-1).

NMR struc:

1 models

Authors:

M.Caffrey,A.Jacobs,L.Guilhaudis

Key ref:

L.Guilhaudis et al. (2002). Solution structure of the HIV gp120 C5 domain. Eur J Biochem, 269, 4860-4867. PubMed id: 12354117 DOI: 10.1046/j.1432-1033.2002.03187.x

Date:

08-Aug-02 Release date: 11-Dec-02

Protein chain

P19549  (ENV_HV1S3) -  Envelope glycoprotein gp160

Seq: 852 a.a.

Struc: 23 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: viral envelope (1 term)

DOI no: 10.1046/j.1432-1033.2002.03187.x

Eur J Biochem 269:4860-4867 (2002)

PubMed id: 12354117

Solution structure of the HIV gp120 C5 domain.

L.Guilhaudis, A.Jacobs, M.Caffrey.

ABSTRACT

In HIV the viral envelope protein is processed by a host cell protease to form gp120 and gp41. The C1 and C5 domains of gp120 are thought to directly interact with gp41 but are largely missing from the available X-ray structure. Biophysical studies of the HIV gp120 C5 domain (residues 489-511 of HIV-1 strain HXB2), which corresponds to the carboxy terminal region of gp120, have been undertaken. CD studies of the C5 domain suggest that it is unstructured in aqueous solutions but partially helical in trifluoroethanol/aqueous and hexafluoroisopropanol/aqueous buffers. The solution structure of the C5 peptide in 40% trifluoroethanol/aqueous buffer was determined by NMR spectroscopy. The resulting structure is a turn helix structural motif, consistent with the CD results. Fluorescence titration experiments suggest that HIV C5 forms a 1 : 1 complex with the HIV gp41 ectodomain in the presence of cosolvent with an apparent Kd of approximately 1.0 micro m. The absence of complex formation in the absence of cosolvent indicates that formation of the turn-helix structural motif of C5 is necessary for complex formation. Examination of the C5 structure provides insight into the interaction between gp120 and gp41 and provides a possible target site for future drug therapies designed to disrupt the gp120/gp41 complex. In addition, the C5 structure lends insight into the site of HIV envelope protein maturation by the host enzymes furin and PC7, which provides other possible targets for drug therapies.

Selected figure(s)

Figure 5.
Fig. 5. (A) Ribbon diagram of the minimized mean structure of HIV gp120 C5 in 40% trifluoroethanol and (B) electrostatic map of the minimized mean structure of HIV gp120 C5.(A) The location of the furin/PC7 site is shown. The locations of the missing gp120 domains and gp41 are denoted. (B) In this orientation, the conserved ‘hydrophobic elbow’ of C5 is located at the upper left corner of the figure.

Figure 7.
Fig. 7. Model for the gp41–gp120 complex upon association with the target cell receptors. The HIV gp41 ectodomain is shown in blue and is a taken from the model structure [33], which is based on the NMR structure of the SIV gp41 ectodomain [18]. The gp120 C5 structure is shown in red and is taken from the present work. The structure of the core gp120-CD4 receptor-antibody 17b complex is taken from Kwong et al. [7]. The gp120 core is shown in green; the CD4 receptor is shown in cyan, and the antibody 17b is shown in violet. The sites of the most reactive non-native cysteines in gp41 (at position 94) and gp120 (atposition 501) are shown as spheres and aretaken from Binley et al. [10].

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2002, 269, 4860-4867) copyright 2002.

Figures were selected by an automated process.