Structural and functional aspects of decorsin and its analog as recognized by integrin αIIbβ3

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• 作者：Xingzhen Lao ; Jingxiao Bao ; Tingting Yu ; Qingqing Li…
• 关键词：Decorsin ; Integrin ; Mutation ; RGD motif
• 刊名：Journal of Molecular Modeling
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：22
• 期：11
• 全文大小：3,151 KB
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Computer Applications in Chemistry
  Biomedicine
  Molecular Medicine
  Health Informatics and Administration
  Life Sciences
  Computer Application in Life Sciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：0948-5023
• 卷排序：22

文摘

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.