NMR structural analysis of a peptide mimic of the bridging sheet of HIV-1 gp120 in methanol and water

Chakraborty, Kausik and Shivakumar, P and Raghothama, S and Varadarajan, Raghavan (2005) NMR structural analysis of a peptide mimic of the bridging sheet of HIV-1 gp120 in methanol and water. In: Biochemical Journal, 390 (Part 2). pp. 573-581.

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Abstract

gp120 is a subunit of the Env (viral envelope protein) of HIV-1. The protein consists of inner and outer domains linked by a bridging sheet. Several gp120 residues that bind the neutralizing antibody 17b as well as the cellular co-receptor CCR5 (CC chemokine receptor 5), are located in the bridging sheet. Peptides that mimic the 17b-binding regions of gp120 would be useful potential immunogens for the generation of neutralizing antibodies against HIV-1. Towards this end, a 26-residue, four-stranded \beta -sheet peptide was designed on the basis of the structure of the bridging sheet, and its structure was characterized in methanol by NMR. In methanol, amide and \alpha -proton resonances were well resolved and dispersed. A number of interstrand NOEs (nuclear Overhauser effects) were observed, providing good evidence for multiple turn \beta -hairpin structure. NOEs also provided good evidence for all Xxx–D-Pro bonds in the trans configuration and all three turns formed by a two residue D-Pro–Gly segment to be of type II_ turn. The structure conforms well to the designed fourstranded \beta -sheet structure. Approx. 20% of the peptide was estimated to adopt a folded conformation in water, as evidenced by CD spectroscopy. This was consistent with smaller, but still significant, downfield shifts of $C^a H$ protons relative to randomcoil values. A second peptide was designed with two disulphide bonds to further constrain the peptide backbone.While structured in methanol, this peptide, like the previous one, also exhibits only partial structure formation in water, as evidenced by CD spectroscopy.

Item Type:	Journal Article
Publication:	Biochemical Journal
Publisher:	Portland Press Ltd
Additional Information:	The copyright for this article belongs to Portland Press Ltd.
Keywords:	CD4i;gp120;HIV;17b;spectroscopy
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	18 Nov 2005
Last Modified:	19 Sep 2010 04:21
URI:	http://eprints.iisc.ac.in/id/eprint/4008

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