Gurudutta Gangenahalli U, Verma Yogesh Kr, Singh Vimal Kishor, Gupta Pallavi, Raj H G, Sharma R K, Chandra Ramesh
Stem Cell Gene Therapy Research Group, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi 110054, India.
FEBS Lett. 2005 Jul 4;579(17):3503-7. doi: 10.1016/j.febslet.2005.05.015.
The sequence of Bcl-2 homology domains, BH1 and BH2, is known to be conserved among anti- and pro-apoptotic members of Bcl-2 family proteins. But structural conservation of these domains with respect to functionally active residues playing role in heterodimerization-mediated regulation of apoptosis has never been elucidated. Here, we have suggested the formation of an active site by structurally conserved residues in BH1 (glycine, arginine) and BH2 (tryptophan) domains of Bcl-2 family members, which also accounts for the functional effect of known mutations in BH1 (G145A, G145E) and BH2 (W188A) domains of Bcl-2.
已知Bcl-2同源结构域BH1和BH2的序列在Bcl-2家族蛋白的抗凋亡和促凋亡成员中是保守的。但这些结构域相对于在异二聚体介导的细胞凋亡调节中起作用的功能活性残基的结构保守性从未得到阐明。在这里，我们提出Bcl-2家族成员的BH1（甘氨酸、精氨酸）和BH2（色氨酸）结构域中结构保守的残基形成了一个活性位点，这也解释了Bcl-2的BH1（G145A、G145E）和BH2（W188A）结构域中已知突变的功能效应。
