pH-dependent Self-association of Influenza Hemagglutinin Fusion Peptides in Lipid Bilayers

2000 ◽  
Vol 304 (5) ◽  
pp. 953-965 ◽  
Author(s):  
Xing Han ◽  
Lukas K. Tamm
Keyword(s):  
Lipid Bilayers ◽  
Fusion Peptides ◽  
Influenza Hemagglutinin ◽  
Ph Dependent ◽  
Self Association

Viral Fusion Peptides: A Tool Set to Disrupt and Connect Biological Membranes

2000 ◽  
Vol 20 (6) ◽  
pp. 501-518 ◽  
Author(s):  
Lukas K. Tamm ◽  
Xing Han
Keyword(s):  
Lipid Bilayers ◽  
Biological Membrane ◽  
Membrane Curvature ◽  
Current Evidence ◽  
Viral Fusion ◽  
Fusion Peptides ◽  
Membrane Surfaces ◽  
Self Association ◽  
Α Helix ◽  
And Function

The structure and function of viral fusion peptides are reviewed. The fusion peptides of influenza virus hemagglutinin and human immunodeficiency virus are used as paradigms. Fusion peptides associated with lipid bilayers are conformationally polymorphic. Current evidence suggests that the fusion-promoting state is the obliquely inserted α-helix. Fusion peptides also have a tendency to self-associate into γ-sheets at membrane surfaces. Although the conformational conversion between α- and γ-states is reversible under controlled conditions, its physiological relevance is not yet known. The energetics of peptide insertion and self-association could be measured recently using more soluble “second generation” fusion peptides. Fusion peptides have been reported to change membrane curvature and the state of hydration of membrane surfaces. The combined results are built into a model for the mechanism by which fusion peptides are proposed to assist in biological membrane fusion.

scholarly journals Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill

2018 ◽  
Vol 115 (34) ◽  
pp. E7905-E7913 ◽  
Author(s):  
Xingcheng Lin ◽  
Jeffrey K. Noel ◽  
Qinghua Wang ◽  
Jianpeng Ma ◽  
José N. Onuchic
Keyword(s):  
Viral Entry ◽  
Large Scale ◽  
Coiled Coil ◽  
Structural Rearrangement ◽  
Structural Heterogeneity ◽  
Host Cells ◽  
Fusion Peptides ◽  
Influenza Hemagglutinin ◽  
Loop Region ◽  
Coil Transition

Influenza hemagglutinin (HA) mediates viral entry into host cells through a large-scale conformational rearrangement at low pH that leads to fusion of the viral and endosomal membranes. Crystallographic and biochemical data suggest that a loop-to-coiled-coil transition of the B-loop region of HA is important for driving this structural rearrangement. However, the microscopic picture for this proposed “spring-loaded” movement is missing. In this study, we focus on understanding the transition of the B loop and perform a set of all-atom molecular dynamics simulations of the full B-loop trimeric structure with the CHARMM36 force field. The free-energy profile constructed from our simulations describes a B loop that stably folds half of the postfusion coiled coil in tens of microseconds, but the full coiled coil is unfavorable. A buried hydrophilic residue, Thr59, is implicated in destabilizing the coiled coil. Interestingly, this conserved threonine is the only residue in the B loop that strictly differentiates between the group 1 and 2 HA molecules. Microsecond-scale constant temperature simulations revealed that kinetic traps in the structural switch of the B loop can be caused by nonnative, intramonomer, or intermonomer β-sheets. The addition of the A helix stabilized the postfusion state of the B loop, but introduced the possibility for further β-sheet structures. Overall, our results do not support a description of the B loop in group 2 HAs as a stiff spring, but, rather, it allows for more structural heterogeneity in the placement of the fusion peptides during the fusion process.

scholarly journals pH-Dependent self-association of the Src homology 2 (SH2) domain of the Src homologous and collagen-like (SHC) protein

1996 ◽  
Vol 5 (3) ◽  
pp. 405-413 ◽  
Author(s):  
Stéphane Réty ◽  
Klaus Fütterer ◽  
Richard A. Grucza ◽  
Consuelo M. Munoz ◽  
William A. Frazier ◽  
...  
Keyword(s):  
Sh2 Domain ◽  
Src Homology 2 ◽  
Src Homology ◽  
Ph Dependent ◽  
Self Association

scholarly journals GPI- and transmembrane-anchored influenza hemagglutinin differ in structure and receptor binding activity

1993 ◽  
Vol 122 (6) ◽  
pp. 1253-1265 ◽  
Author(s):  
GW Kemble ◽  
YI Henis ◽  
JM White
Keyword(s):  
Cell Surface ◽  
Receptor Binding ◽  
Conformational Changes ◽  
Binding Pocket ◽  
Binding Activity ◽  
Great Distance ◽  
Fusion Peptides ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
Receptor Binding Activity

We investigated the influence of a glycosylphosphatidylinositol (GPI) anchor on the ectodomain of the influenza hemagglutinin (HA) by replacing the wild type (wt) transmembrane and cytoplasmic domains with a GPI lipid anchor. GPI-anchored HA (GPI-HA) was transported to the cell surface with equal efficiency and at the same rate as wt-HA. Like wt-HA, cell surface GPI-HA, and its ectodomain released with the enzyme PI-phospholipase C (PI-PLC), were 9S trimers. Compared to wt-HA, the GPI-HA ectodomain underwent additional terminal oligosaccharide modifications; some of these occurred near the receptor binding pocket and completely inhibited the ability of GPI-HA to bind erythrocytes. Growth of GPI-HA-expressing cells in the presence of the mannosidase I inhibitor deoxymannojirimycin (dMM) abrogated the differences in carbohydrate modification and restored the ability of GPI-HA to bind erythrocytes. The ectodomain of GPI-HA produced from cells grown in the presence or absence of dMM underwent characteristic low pH-induced conformational changes (it released its fusion peptides and became hydrophobic and proteinase sensitive) but at 0.2 and 0.4 pH units higher than wt-HA, respectively. These results demonstrate that although GPI-HA forms a stable trimer with characteristics of the wt, its structure is altered such that its receptor binding activity is abolished. Our results show that transmembrane and GPI-anchored forms of the same ectodomain can exhibit functionally important differences in structure at a great distance from the bilayer.

scholarly journals Plasticity and conformational equilibria of influenza fusion peptides in model lipid bilayers

2014 ◽  
Vol 1838 (4) ◽  
pp. 1169-1179 ◽  
Author(s):  
Neil R. Haria ◽  
Luca Monticelli ◽  
Franca Fraternali ◽  
Christian D. Lorenz
Keyword(s):  
Lipid Bilayers ◽  
Fusion Peptides ◽  
Conformational Equilibria
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