title: Contribution of the CR domain to P-selectin lectin domain allostery by regulating the orientation of the EGF domain.
abstract: The allostery of P-selectin has been studied extensively with a focus on the Lec and EGF domains, whereas the contribution of the CR domain remains unclear. Here, molecular dynamics simulations (MDS) combined with homology modeling were preformed to investigate the impact of the CR domain on P-selectin allostery. The results indicated that the CR domain plays a role in the allosteric dynamics of P-selectin in two ways. First, the CR1 domain tends to stabilize the low affinity of P-selectin during the equilibration processes with the transition inhibition from the S1 to S1' state by restraining the extension of the bent EGF orientation, or with the relaxation acceleration of the S2 state by promoting the bending of the extended EGF orientation. Second, the existence of CR domain increases intramolecular extension prior to complex separation, increasing the time available for the allosteric shift during forced dissociation with a prolonged bond duration. These findings further our understanding of the structure-function relationship of P-selectin with the enriched micro-structural bases of the CR domain.
authors: Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
authors: Shouqin
authors: S
authors: Lü
authors: Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
authors: Shenbao
authors: S
authors: Chen
authors: Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
authors: Debin
authors: D
authors: Mao
authors: Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
authors: Yan
authors: Y
authors: Zhang
authors: Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China; Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
authors: Mian
authors: M
authors: Long
mesh_terms: D000494:Allosteric Regulation; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019007:P-Selectin / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D013329:Structure-Activity Relationship
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein