1jav
From Proteopedia
(New page: 200px<br /> <applet load="1jav" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jav" /> '''AVERAGE NMR SOLUTION STRUCTURE OF THE TRP-R...) |
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'''AVERAGE NMR SOLUTION STRUCTURE OF THE TRP-RICH PEPTIDE OF HIV GP41 BOUND TO DPC MICELLES'''<br /> | '''AVERAGE NMR SOLUTION STRUCTURE OF THE TRP-RICH PEPTIDE OF HIV GP41 BOUND TO DPC MICELLES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The membrane-proximal tryptophan-rich region of the HIV transmembrane | + | 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== | ==About this Structure== | ||
| - | 1JAV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1JAV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JAV OCA]. |
==Reference== | ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11583156 11583156] | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11583156 11583156] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Montelaro, R | + | [[Category: Montelaro, R C.]] |
| - | [[Category: Schibli, D | + | [[Category: Schibli, D J.]] |
| - | [[Category: Vogel, H | + | [[Category: Vogel, H J.]] |
[[Category: NH2]] | [[Category: NH2]] | ||
[[Category: amphipathic alpha helix]] | [[Category: amphipathic alpha helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:20:33 2008'' |
Revision as of 11:20, 21 February 2008
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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 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
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