Characterizing the binding of annexin V to a lipid bilayer using molecular dynamics simulations.
Annexins play critical roles in membrane organization, membrane trafficking and vesicle transport. The family members share the ability to bind to membranes with high affinities, but the interactions between annexins and membranes remain unclear. Here, using long-time molecular dynamics simulations, we provide detailed information for the binding of an annexin V trimer to a POPC/POPS lipid bilayer. Calcium ions function as bridges between several negatively charged residues of annexin V and the oxygen atoms of lipids. The preferred calcium-bridges are those formed via the carboxyl oxygen atoms of POPS lipids. H-bonds and hydrophobic interactions formed by several critical residues have also been observed in the annexin-membrane interface. The annexin-membrane binding causes small changes of annexin trimer structures, while has significant effects on lipid bilayer structures. The lipid bilayer shows a bent shape and forms a concave region in the annexin-membrane interaction interface, which provides an atomic-level evidence to support the view that annexins could disturb the stability of lipids and bend membranes. This study provides insights into the commonly occurring PS-dependent and calcium-dependent binding of proteins to membranes.
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Zhuxi
Z
Chen
Yanyan
Y
Mao
Jing
J
Yang
Tao
T
Zhang
Lifen
L
Zhao
Kunqian
K
Yu
Mingyue
M
Zheng
Hualiang
H
Jiang
Huaiyu
H
Yang
D017304:Annexin A5 / Q000737:chemistry*; D002118:Calcium; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D011485:Protein Binding; D055550:Protein Stability
D017304:Annexin A5; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; D002118:Calcium; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
POPS; annexin V trimer; calcium; calcium-bridge; membrane