Journal
BIOCHEMISTRY
Volume 48, Issue 23, Pages 5090-5095Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi900435m
Keywords
-
Categories
Funding
- BBSRC
- EPSRC
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council [B19456, BBS/B/16011, BEP17032, BB/H000267/1] Funding Source: researchfish
- BBSRC [BB/H000267/1] Funding Source: UKRI
Ask authors/readers for more resources
Molecular dynamics simulations have been used to explore the interactions of two PI(3)P-binding domains with their PI ligands and with a phospholipid bilayer. Three simulations each of the EEA1-FYVE domain and the p40(phox)-PX domain have been compared: with the protein in an apo state, with a bound Ins (1,3)P-2 molecule, and bound to a PI(3)P molecule embedded in a lipid bilayer. Two main questions were addressed in analysis of the simulations: (i) the location of these domains relative to the lipid bilayer and (ii) their interactions with the lipids, both specific interactions via bound PI(3)P and nonspecific interactions with bilayer phospho lipids. Both domains underwent a decrease in dynamic flexibility on binding to the ligand and to the membrane, this being more pronounced for the FYVE domain. Compared to their starting locations [docked to a membrane-inserted PI(3)P molecule], each of the domains penetrated more deeply into the lipid bilayer. For FYVE, nonspecific protein-lipid interactions were formed mainly by the N-terminal hydrophobic region of the protein. For PX, both the alpha 1-alpha 2 and the beta 1-beta 2 regions penetrated the bilayer. There appeared to be more marked dynamic fluctuations in hydrogen bonds between basic side chains and PI(3)P for FYVE than for PX, but for both domains, such interactions were maintained throughout the simulations. The simulations agree well with available biophysical data, suggesting this computational method may be used to predict protein-bilayer interactions for other PI-binding proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available