-

nihao guest [ sign in / register ]
2024-5-11 23:00:15


Lin X, Noel JK, Wang Q, Ma J, et al. Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill. Proc Natl Acad Sci U S A 2018 Jul 16.
submited by kickingbird at Jul, 23, 2018 10:44 AM from Proc Natl Acad Sci U S A 2018 Jul 16.

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.

See Also:

Latest articles in those days:

[Go Top]    [Close Window]

Related Pages:
Learn about the flu news, articles, events and more
Subscribe to the weekly F.I.C newsletter!


  

Site map  |   Contact us  |  Term of use  |  FAQs |  粤ICP备10094839号-1
Copyright ©www.flu.org.cn. 2004-2024. All Rights Reserved. Powered by FIC 4.0.1
  Email:webmaster@flu.org.cn