3F50

HIV gp41 six-helix bundle composed of an alpha/beta-peptide analogue of the CHR domain in complex with an NHR domain alpha-peptide

Summary for 3F50

• Entry DOI: 10.2210/pdb3f50/pdb
• Related: 3F4Y 3F4Z
• Descriptor: Envelope glycoprotein gp160, alpha/beta-peptide analogue of the HIV gp41 CHR domain, GLYCEROL, ... (4 entities in total)
• Functional Keywords: alpha/beta-peptide, helix bundle, viral protein, aids, apoptosis, cell membrane, cleavage on pair of basic residues, envelope protein, fusion protein, glycoprotein, host-virus interaction, lipoprotein, membrane, palmitate, transmembrane, viral immunoevasion, virion
• Cellular location: Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: 3F50
• Total number of polymer chains: 2
• Total formula weight: 8769.03

Authors

Horne, W.S.,Gellman, S.H. (deposition date: 2008-11-03, release date: 2009-09-15, Last modification date: 2023-11-15)

Primary citation

Horne, W.S.,Johnson, L.M.,Ketas, T.J.,Klasse, P.J.,Lu, M.,Moore, J.P.,Gellman, S.H.
Structural and biological mimicry of protein surface recognition by alpha/beta-peptide foldamers
Proc.Natl.Acad.Sci.USA, 106:14751-14756, 2009

PubMed Abstract: Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining alpha- and beta-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that alpha/beta-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic alpha/beta-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived alpha-peptides. An optimized alpha/beta-peptide is far less susceptible to proteolytic degradation than is an analogous alpha-peptide. Our findings show how a two-stage design approach, in which sequence-based alpha-->beta replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.

PubMed: 19706443
DOI: 10.1073/pnas.0902663106

Experimental method

X-RAY DIFFRACTION (2.8 Å)