scholarly journals Studies of the membrane fusion activities of fusion peptide mutants of influenza virus hemagglutinin.

1995 ◽  
Vol 69 (11) ◽  
pp. 6643-6651 ◽  
Author(s):  
D A Steinhauer ◽  
S A Wharton ◽  
J J Skehel ◽  
D C Wiley
2005 ◽  
Vol 79 (18) ◽  
pp. 12065-12076 ◽  
Author(s):  
Yinling Li ◽  
Xing Han ◽  
Alex L. Lai ◽  
John H. Bushweller ◽  
David S. Cafiso ◽  
...  

ABSTRACT Influenza virus hemagglutinin (HA)-mediated membrane fusion is initiated by a conformational change that releases a V-shaped hydrophobic fusion domain, the fusion peptide, into the lipid bilayer of the target membrane. The most N-terminal residue of this domain, a glycine, is highly conserved and is particularly critical for HA function; G1S and G1V mutant HAs cause hemifusion and abolish fusion, respectively. We have determined the atomic resolution structures of the G1S and G1V mutant fusion domains in membrane environments. G1S forms a V with a disrupted “glycine edge” on its N-terminal arm and G1V adopts a slightly tilted linear helical structure in membranes. Abolishment of the kink in G1V results in reduced hydrophobic penetration of the lipid bilayer and an increased propensity to formβ -structures at the membrane surface. These results underline the functional importance of the kink in the fusion peptide and suggest a structural role for the N-terminal glycine ridge in viral membrane fusion.


2002 ◽  
Vol 76 (9) ◽  
pp. 4456-4466 ◽  
Author(s):  
Jennifer A. Gruenke ◽  
R. Todd Armstrong ◽  
William W. Newcomb ◽  
Jay C. Brown ◽  
Judith M. White

ABSTRACT Influenza virus hemagglutinin undergoes a conformational change in which a loop-to-helix “spring-loaded” conformational change forms a coiled coil that positions the fusion peptide for interaction with the target bilayer. Previous work has shown that two proline mutations designed to disrupt this change disrupt fusion but did not determine the basis for the fusion defect. In this work, we made six additional mutants with single proline substitutions in the region that undergoes the spring-loaded conformational change and two additional mutants with double proline substitutions in this region. All double mutants were fusion inactive. We analyzed one double mutant, F63P/F70P, as an example. We observed that F63P/F70P undergoes key low-pH-induced conformational changes and binds tightly to target membranes. However, limited proteolysis and electron microscopy observations showed that the mutant forms a coiled coil that is only ∼50% the length of the wild type, suggesting that it is splayed in its N-terminal half. This work further supports the hypothesis that the spring-loaded conformational change is necessary for fusion. Our data also indicate that the spring-loaded conformational change has another role beyond presenting the fusion peptide to the target membrane.


2002 ◽  
Vol 277 (25) ◽  
pp. 22725-22733 ◽  
Author(s):  
Chun-Hua Hsu ◽  
Shih-Hsiung Wu ◽  
Ding-Kwo Chang ◽  
Chinpan Chen

Biochemistry ◽  
2014 ◽  
Vol 53 (5) ◽  
pp. 846-854 ◽  
Author(s):  
Fengyun Ni ◽  
Xiaorui Chen ◽  
Jun Shen ◽  
Qinghua Wang

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