title: Structural and functional aspects of decorsin and its analog as recognized by integrin αIIbβ3.
abstract: Decorsin is an antagonist of platelet glycoprotein integrin αIIbβ3 on platelets; the protein is 39 amino acids long with three disulfide bridges in its tertiary structure. To demonstrate decorsin's mechanism of action, we applied the computational virtual technique and platelet aggregation inhibition assay, which showed that the flanking amino-acid residues of the Arg-Gly-Asp (RGD) motif play an important role in platelet aggregation. The computational simulations revealed that the RGD motif mainly contributes to the stability of the complex when decorsion interacts with integrin αIIbβ3. However, the C-terminal residues, such as 34A→W and 35D→R, was also found to possibly play a key role in their binding structures. Moreover, we produced a decorsin analog (A34W plus D35R decorsin), in which the 34A (alanine) and 35D (aspartic acid) residues were respectively substituted by W (tryptophan) and R (arginine). This isoform was then recombinantly expressed in Escherichia coli. Intriguingly, this mutant type showed higher anti-platelet aggregation activity than the wildtype. Our study may further contribute to finding decorsin mutants with higher anti-platelet aggregation activity.
authors: School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
authors: Xingzhen
authors: X
authors: Lao
authors: School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
authors: Jingxiao
authors: J
authors: Bao
authors: School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
authors: Tingting
authors: T
authors: Yu
authors: School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
authors: Qingqing
authors: Q
authors: Li
authors: School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China. cpu_zhengheng@163.com.
authors: Heng
authors: http://orcid.org/0000-0002-4601-6425
authors: H
authors: Zheng
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D015815:Cell Adhesion Molecules; D006801:Humans; D056004:Molecular Dynamics Simulation; D020125:Mutation, Missense; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011506:Proteins; D011994:Recombinant Proteins; C064478:decorsin
keywords: Decorsin; Integrin; Mutation; RGD motif