Mechanobiology Institute Singapore, 5A Engineering Drive 1, National University of Singapore, 117411 Singapore, Singapore.
FEBS Lett. 2012 Aug 14;586(17):2674-91. doi: 10.1016/j.febslet.2012.04.023. Epub 2012 Apr 21.
The BNIP-2 and Cdc42GAP Homology (BCH) domains constitute a new and expanding family of highly conserved scaffold protein domains that regulate Rho, Ras and MAPK signaling, leading to cell growth, apoptosis, morphogenesis, migration and differentiation. Such versatility is achieved via their ability to target small GTPases and their immediate regulators such as GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), their ability to form intra-molecular or inter-molecular interaction with itself or with other BCH domains, and also by their ability to bind diverse cellular proteins such as membrane receptors, isomerase, caspases and metabolic enzymes such as glutaminase. The presence of BCH and BCH-like domains in various proteins and their divergence from the ancestral lipid-binding CRAL-TRIO domain warrant the need to examine closely their structural, functional and regulatory plasticity in isolation or in concert with other protein modules present in the same proteins.
BNIP-2 和 Cdc42GAP 同源（BCH）结构域构成了一个新的、不断扩展的高度保守支架蛋白结构域家族，该家族可调节 Rho、Ras 和 MAPK 信号通路，从而导致细胞生长、凋亡、形态发生、迁移和分化。这种多功能性是通过其靶向小 GTPase 及其直接调节因子（如 GTPase 激活蛋白（GAP）和鸟苷酸交换因子（GEF））的能力、其形成分子内或分子间相互作用自身或与其他 BCH 结构域的能力，以及与各种细胞蛋白如膜受体、异构酶、半胱天冬酶和代谢酶如谷氨酰胺酶结合的能力来实现的。各种蛋白质中存在 BCH 和 BCH 样结构域，且它们与祖先脂质结合的 CRAL-TRIO 结构域不同，这就需要仔细研究它们的结构、功能和调节的可塑性，无论是单独研究还是与同一蛋白质中存在的其他蛋白质模块协同研究。
