Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.
J Comput Chem. 2020 Nov 15;41(30):2544-2561. doi: 10.1002/jcc.26407. Epub 2020 Sep 15.
In Glioblastoma (GBM) brain tumors, both Gremlin-1 and Noggin are reported to bind to BMP and inhibit BMP-signaling, thereby allowing the cell to maintain tumorous morphology. Enlisting the interfacial residues important for protein-protein complex formation between BMPs (BMP-2 and BMP-7) and antagonists (Gremlin-1 and Noggin), we analyzed the structural basis of their interactions. We found possible key mutations that destabilize these complexes, which may prevent GBM development. It was also observed that when the interfacial residues were either mutated to histidine or tryptophan, it led to higher destabilization energy values. Besides, our study of the Noggin interactive model of BMP-2 suggested preferential binding at binding site II over binding site I. In the case of Gremlin-1 and BMPs, our research, along with few previous studies, indicates a close-ended cis-trans interactive model.
在神经胶质瘤（GBM）脑肿瘤中，报道称 Gremlin-1 和 Noggin 都与 BMP 结合并抑制 BMP 信号通路，从而使细胞保持肿瘤形态。我们利用 BMPs（BMP-2 和 BMP-7）和拮抗剂（Gremlin-1 和 Noggin）之间形成蛋白-蛋白复合物的界面残基，分析了它们相互作用的结构基础。我们发现了可能导致这些复合物不稳定的关键突变，这可能阻止 GBM 的发展。还观察到，当界面残基突变为组氨酸或色氨酸时，会导致更高的不稳定能值。此外，我们对 Noggin 与 BMP-2 相互作用模型的研究表明，在结合位点 II 上的优先结合优于结合位点 I。对于 Gremlin-1 和 BMPs，我们的研究以及一些以前的研究表明，存在一种封闭的顺式-反式相互作用模型。
