Mace Peter D, Cutfield John F, Cutfield Sue M
Department of Biochemistry, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9001, New Zealand.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):831-8. doi: 10.1016/j.bbrc.2006.10.109. Epub 2006 Nov 10.
BMPRII is a type II TGF-beta serine threonine kinase receptor which is integral to the bone morphogenetic protein (BMP) signalling pathway. It is known to bind BMP and growth differentiation factor (GDF) ligands, and has overlapping ligand specificity with the activin type II receptor, ActRII. In contrast to activin and TGF-beta type ligands, BMPs bind to type II receptors with lower affinity than type I receptors. Crystals of the BMPRII ectodomain were grown in two different forms, both of which diffracted to high resolution. The tetragonal form exhibited some disorder, whereas the entire polypeptide was seen in the orthorhombic form. The two structures retain the basic three-finger toxin fold of other TGF-beta receptor ectodomains, and share the main hydrophobic patch used by ActRII to bind various ligands. However, they present different conformations of the A-loop at the periphery of the proposed ligand-binding interface, in conjunction with rearrangement of a disulfide bridge within the loop. This particular disulfide (Cys94-Cys117) is only present in BMPRII and activin receptors, suggesting that it is important for their likely shared mode of binding. Evidence is presented that the two crystal forms represent ligand-bound and free conformations of BMPRII. Comparison with the solved structure of ActRII bound to BMP2 suggests that His87, unique amongst TGF-beta receptors, may play a key role in ligand recognition.
骨形态发生蛋白受体II（BMPRII）是一种II型转化生长因子β（TGF-β）丝氨酸苏氨酸激酶受体，是骨形态发生蛋白（BMP）信号通路不可或缺的一部分。已知它能结合BMP和生长分化因子（GDF）配体，并且与激活素II型受体ActRII具有重叠的配体特异性。与激活素和TGF-β型配体不同，BMP与II型受体结合的亲和力低于I型受体。BMPRII胞外域的晶体以两种不同形式生长，两种形式均能衍射到高分辨率。四方晶型表现出一些无序，而在正交晶型中可看到完整的多肽。这两种结构保留了其他TGF-β受体胞外域基本的三指毒素折叠结构，并且共享ActRII用于结合各种配体的主要疏水区域。然而，它们在可能的配体结合界面外围呈现出A环的不同构象，同时环内二硫键发生重排。这个特定的二硫键（Cys94-Cys117）仅存在于BMPRII和激活素受体中，表明它对于它们可能的共同结合模式很重要。有证据表明这两种晶体形式分别代表BMPRII的配体结合构象和游离构象。与已解析的ActRII与BMP2结合的结构进行比较表明，His87在TGF-β受体中是独特的，可能在配体识别中起关键作用。
