1jav
From Proteopedia
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AVERAGE NMR SOLUTION STRUCTURE OF THE TRP-RICH PEPTIDE OF HIV GP41 BOUND TO DPC MICELLES
Overview
The membrane-proximal tryptophan-rich region of the HIV transmembrane, glycoprotein, gp41, plays an important role in the membrane fusion, reaction. Using NMR spectroscopy, we have studied the tertiary structure, of a synthetic 19-residue amidated peptide (NH2-KWASLWNWFNITNWLWYIK-CONH2), corresponding to this region in membrane-mimetic environments. Initial, experiments in sodium dodecyl sulfate/H2O micelles and trifluoroethanol, gave poor results, because of low solubility. However, in, dodecylphosphocholine micelles, we obtained excellent 500 and 800 MHz NMR, spectra, suggesting that the peptide has a preference for a zwitterionic, membrane-like environment. The final NMR structures demonstrated a, well-defined helical peptide with a backbone rmsd of 0.47 +/- 0.18 A. Four, of the five tryptophan residues, as well as the tyrosine residue, formed a, "collar" of aromatic residues along the axial length of the helix. By, analogy to related tryptophan-rich antimicrobial peptides, the structure, indicates that the aromatic residues of the HIV peptide are positioned, within the membrane-water interface of a phospholipid bilayer. This is, confirmed by the observation of direct NOEs between the aromatic residues, of the peptide to the headgroup and interfacial protons of prototonated, dodecylphosphocholine. The bulk of the polar residues are positioned on, one face of this structure, with the hydrophobic phenylalanine side chain, on the opposing face, forming an amphipathic structure. This work shows, that the Trp-rich membrane-proximal region of HIV and related viruses can, bind to the surfaces of zwitterioninc membranes in a "Velcro-like" manner.
About this Structure
1JAV is a Single protein structure of sequence from [1] with NH2 as ligand. Full crystallographic information is available from OCA.
Reference
The membrane-proximal tryptophan-rich region of the HIV glycoprotein, gp41, forms a well-defined helix in dodecylphosphocholine micelles., Schibli DJ, Montelaro RC, Vogel HJ, Biochemistry. 2001 Aug 14;40(32):9570-8. PMID:11583156
Page seeded by OCA on Thu Nov 8 14:11:55 2007
