2jrd
From Proteopedia
(New page: 200px<br /><applet load="2jrd" size="350" color="white" frame="true" align="right" spinBox="true" caption="2jrd" /> '''Influenza Hemagglutinin Fusion Domain Mutant...) |
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==Overview== | ==Overview== | ||
| - | We have previously identified Trp(14) as a critical residue that | + | We have previously identified Trp(14) as a critical residue that stabilizes the kink in the boomerang structure of the influenza fusion domain and found that cells expressing hemagglutinin with a Trp(14) to Ala mutation cannot fuse with red blood cells. However, mutating another aromatic residue, Phe(9), on the other side of the kink did not have a significant effect on fusion or the ability of the mutant fusion peptide to bind to or perturb the bilayer structure of lipid model membranes. We reasoned that Phe is not as potent to contribute to the kink as the larger Trp and that the cooperation of Phe(9) and Ile(10) might be needed to elicit the same effect. Indeed, the double mutant F9A/I10A diminished cell-cell fusion and the ability of the fusion domain to bind to and perturb lipid bilayers in a similar fashion as the W14A mutant. A structure determination of F9A in lipid micelles by solution NMR shows that F9A adopts a similarly kinked structure as wild type. Distances between the two arms of the boomerang structure of wild type, F9A, W14A, and F9A/I10A in lipid bilayers were measured by double electron-electron resonance spectroscopy and showed that the kinks of W14A and F9A/I10A are more flexible than those of wild type and F9A. These results underscore the importance of large hydrophobic residues on both sides of the kink region of the influenza hemagglutinin fusion domain to fix the angle of the boomerang structure and thereby confer fusion function to this critical domain. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Influenza a virus]] | [[Category: Influenza a virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Lai, A | + | [[Category: Lai, A L.]] |
| - | [[Category: Tamm, L | + | [[Category: Tamm, L K.]] |
[[Category: f9a]] | [[Category: f9a]] | ||
[[Category: fusion domain]] | [[Category: fusion domain]] | ||
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[[Category: solution nmr]] | [[Category: solution nmr]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:05:22 2008'' |
Revision as of 16:05, 21 February 2008
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Influenza Hemagglutinin Fusion Domain Mutant F9A
Overview
We have previously identified Trp(14) as a critical residue that stabilizes the kink in the boomerang structure of the influenza fusion domain and found that cells expressing hemagglutinin with a Trp(14) to Ala mutation cannot fuse with red blood cells. However, mutating another aromatic residue, Phe(9), on the other side of the kink did not have a significant effect on fusion or the ability of the mutant fusion peptide to bind to or perturb the bilayer structure of lipid model membranes. We reasoned that Phe is not as potent to contribute to the kink as the larger Trp and that the cooperation of Phe(9) and Ile(10) might be needed to elicit the same effect. Indeed, the double mutant F9A/I10A diminished cell-cell fusion and the ability of the fusion domain to bind to and perturb lipid bilayers in a similar fashion as the W14A mutant. A structure determination of F9A in lipid micelles by solution NMR shows that F9A adopts a similarly kinked structure as wild type. Distances between the two arms of the boomerang structure of wild type, F9A, W14A, and F9A/I10A in lipid bilayers were measured by double electron-electron resonance spectroscopy and showed that the kinks of W14A and F9A/I10A are more flexible than those of wild type and F9A. These results underscore the importance of large hydrophobic residues on both sides of the kink region of the influenza hemagglutinin fusion domain to fix the angle of the boomerang structure and thereby confer fusion function to this critical domain.
About this Structure
2JRD is a Single protein structure of sequence from Influenza a virus. Full crystallographic information is available from OCA.
Reference
Locking the kink in the influenza hemagglutinin fusion domain structure., Lai AL, Tamm LK, J Biol Chem. 2007 Aug 17;282(33):23946-56. Epub 2007 Jun 12. PMID:17567572
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