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

Chakraborty, Kausik ; Shivakumar, P. ; Raghothama, S. ; Varadarajan, Raghavan (2005) NMR structural analysis of a peptide mimic of the bridging sheet of HIV-1 gp120 in methanol and water Biochemical Journal, 390 . pp. 573-581. ISSN 0264-6021

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Official URL: http://www.biochemj.org/bj/390/bj3900573.htm

Related URL: http://dx.doi.org/10.1042/BJ20050442


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 β-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 α-proton resonances were well resolved and dispersed. A number of interstrand NOEs (nuclear Overhauser effects) were observed, providing good evidence for multiple turn β-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 four-stranded b-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 CαH protons relative to random-coil 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:Article
Source:Copyright of this article belongs to Portland Press.
Keywords:CD4i; Gp120; HIV; 17b; Spectroscopy
ID Code:57290
Deposited On:26 Aug 2011 04:19
Last Modified:26 Aug 2011 04:19

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