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- Title
Conformational Stability Analyses of Alpha Subunit I Domain of LFA-1 and Mac-1.
- Authors
Mao, Debin; Lü, Shouqin; Li, Ning; Zhang, Yan; Long, Mian
- Abstract
ß2 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 a7-helix with different motifs of zipper-like hydrophobic junction between a1- and a7-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.
- Subjects
LYMPHOCYTE function-associated antigen-1; MACROPHAGE-1 antigen; INTEGRINS; CELL adhesion molecules; MOLECULAR dynamics; LIGAND binding (Biochemistry); STATISTICAL correlation; CHEMICAL affinity
- Publication
PLoS ONE, 2011, Vol 6, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0024188