Paper Citing NAMD - Abstract
Mao, Debin; Lu, Shouqin; Li, Ning; Zhang, Yan; Long, Mian
Conformational Stability Analyses of Alpha Subunit I Domain of LFA-1 and Mac-1
PLOS ONE, 6 Art. No. e24188, AUG 31 2011
beta(2) integrin of lymphocyte function-associated antigen-1 (LFA-1) or macrophage-1 antigen (Mac-1) binds to their common ligand of intercellular adhesion molecule-1 (ICAM-1) and mediates leukocyte-endothelial cell (EC) adhesions in inflammation cascade. Although the two integrins are known to have distinct functions, the corresponding micro-structural bases remain unclear. Here (steered-)molecular dynamics simulations were employed to elucidate the conformational stability of a subunit I domains of LFA-1 and Mac-1 in different affinity states and relevant I domain-ICAM-1 interaction features. Compared with low affinity (LA) Mac-1, the LA LFA-1 I domain was unstable in the presence or absence of ICAM-1 ligand, stemming from diverse orientations of its alpha(7)-helix with different motifs of zipper-like hydrophobic junction between alpha(1)- and alpha(7)-helices. Meanwhile, spontaneous transition of LFA-1 I domain from LA state to intermediate affinity (IA) state was first visualized. All the LA, IA, and high affinity (HA) states of LFA-1 I domain and HA Mac-1 I domain were able to bind to ICAM-1 ligand effectively, while LA Mac-1 I domain was unfavorable for binding ligand presumably due to the specific orientation of S144 side-chain that capped the MIDAS ion. These results furthered our understanding in correlating the structural bases with their functions of LFA-1 and Mac-1 integrins from the viewpoint of I domain conformational stability and of the characteristics of I domain-ICAM-1 interactions.
