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2jpx

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[[Image:2jpx.jpg|left|200px]]
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[[Image:2jpx.png|left|200px]]
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{{STRUCTURE_2jpx| PDB=2jpx | SCENE= }}
{{STRUCTURE_2jpx| PDB=2jpx | SCENE= }}
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'''A18H Vpu TM structure in lipid bilayers'''
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===A18H Vpu TM structure in lipid bilayers===
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==Overview==
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The channel-forming trans-membrane domain of Vpu (Vpu TM) from HIV-1 is known to enhance virion release from the infected cells and is a potential target for ion-channel blockers. The substitution of alanine at position 18 by a histidine (A18H) has been shown to render HIV-1 infections susceptible to rimantadine, a channel blocker of M2 protein from the influenza virus. In order to describe the influence of the mutation on the structure and rimantadine susceptibility of Vpu, we determined the structure of A18H Vpu TM, and compared it to those of wild-type Vpu TM and M2 TM. Both isotropic and orientationally dependent NMR frequencies of the backbone amide resonance of His18 were perturbed by rimantadine, and those of Ile15 and Trp22 were also affected, suggesting that His18 is the key residue for rimantadine binding and that residues located on the same face of the TM helix are also involved. A18H Vpu TM has an ideal, straight alpha-helix spanning residues 6-27 with an average tilt angle of 41 degrees in C14 phospholipid bicelles, indicating that the tilt angle is increased by 11 degrees compared to that of wild-type Vpu TM. The longer helix formed by the A18H mutation has a larger tilt angle to compensate for the hydrophobic mismatch with the length of the phospholipids in the bilayer. These results demonstrate that the local change of the primary structure plays an important role in secondary and tertiary structures of Vpu TM in lipid bilayers and affects its ability to interact with channel blockers.
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{{ABSTRACT_PUBMED_17766368}}
==About this Structure==
==About this Structure==
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2JPX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JPX OCA].
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2JPX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JPX OCA].
==Reference==
==Reference==
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[[Category: Trans-membrane]]
[[Category: Trans-membrane]]
[[Category: Viral protein]]
[[Category: Viral protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:10:12 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:26:47 2008''

Revision as of 10:26, 27 July 2008

Image:2jpx.png

Template:STRUCTURE 2jpx

A18H Vpu TM structure in lipid bilayers

Template:ABSTRACT PUBMED 17766368

About this Structure

2JPX is a Single protein structure of sequence from Human immunodeficiency virus 1. Full experimental information is available from OCA.

Reference

Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: implications for HIV-1 susceptibility to channel blocking drugs., Park SH, Opella SJ, Protein Sci. 2007 Oct;16(10):2205-15. Epub 2007 Aug 31. PMID:17766368

Page seeded by OCA on Sun Jul 27 13:26:47 2008

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