Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, Institut de Biologie et de Technologies de Saclay, Service d'Ingénierie Moléculaire des Protéines, Bat. 152, 91191 Gif-sur-Yvette, France.
Cell Mol Life Sci. 2011 Oct;68(20):3437-51. doi: 10.1007/s00018-011-0643-4. Epub 2011 Mar 3.
The transforming growth factor-β (TGFβ) superfamily of proteins and their receptors are crucial developmental factors for all metazoan organisms. Cystine-knot (CK) motif is a spatial feature of the TGFβ superfamily of proteins whereas the extra-cellular domains (ectodomains) of their respective receptors form three-fingered protein domain (TFPD), both stabilized by tight cystine networks. Analyses of multiple sequence alignments of these two domains encoded in various genomes revealed that the cystines forming the CK and TFPD folds are conserved, whereas the remaining polypeptide patches are diversified. Orthologues of the human TGFβs and their respective receptors expressed in diverse vertebrates retain high sequence conservation. Examination of 3D structures of various TGFβ factors bound to their receptors have revealed that the CK and TFPD domains display several similar spatial traits suggesting that these two different protein folds might have been acquired from a common ancestor.
转化生长因子-β（TGFβ）蛋白超家族及其受体是所有后生动物发育的关键因素。半胱氨酸结（CK）基序是 TGFβ 蛋白超家族的空间特征，而其各自受体的细胞外结构域（ectodomains）形成三指蛋白结构域（TFPD），两者均由紧密的半胱氨酸网络稳定。对不同基因组中编码这两个结构域的多种序列比对的分析表明，形成 CK 和 TFPD 折叠的半胱氨酸是保守的，而其余的多肽补丁则是多样化的。在不同的脊椎动物中表达的人类 TGFβs 及其各自的受体的同源物保留了高度的序列保守性。对与受体结合的各种 TGFβ 因子的 3D 结构的检查表明，CK 和 TFPD 结构域显示出几个相似的空间特征，这表明这两种不同的蛋白质折叠可能是从一个共同的祖先获得的。
