Allostery of P-selectin lectin (Lec) domain followed by an epithelial growth factor (EGF)-like domain is essential for its biological functionality, but the underlying pathways have not been well understood.
Here the molecular dynamics simulations were performed by Shouqin Lϋ, Yan Zhang, and Mian Long, at Key Laboratory of Microgravity, Chinese Academy of Sciences and Center of Biomechanics and Bioengineering, IMECH, CAS, on the crystallized structures to visualize the dynamic conformational change for state 1 (S1) or state 2 (S2) Lec domain with respective bent (B) or extended (E) EGF orientation. Simulations illustrated that both S1 and S2 conformations were unable to switch from one to another directly. Instead, a novel S1' conformation was observed from S1 when crystallized B-S1 or reconstructed "E-S1" structure was employed, which was superposed well with that of equilibrated S1 Lec domain alone. It was also indicated that the corresponding allosteric pathway from S1 to S1' conformation started with the separation between residues Q30 and K67 and terminated with the release of residue N87 from residue C109. These results provided an insight into understanding the structural transition and the structure-function relationship of P-selectin allostery.
This paper was published as:
Shouqin Lϋ, Yan Zhang, and Mian Long. Visualization of Allostery in P-Selectin Lectin Domain Using MD Simulations. PLOS ONE, 2010, 5(12), e15417. DOI: 10.1371/journal.pone.0015417
Fig. Conformational change of P-selectin Lectin domain