Weidler M, Marx U C, Seidel G, Schäfer W, Hoffmann E, Esswein A, Rösch P
Lehrstuhl für Biopolymere, Universität Bayreuth, Germany.
FEBS Lett. 1999 Feb 12;444(2-3):239-44. doi: 10.1016/s0014-5793(98)01658-5.
Parathyroid hormone-related protein plays a major role in the pathogenesis of humoral hypercalcemia of malignancy. Under normal physiological conditions, parathyroid hormone-related protein is produced in a wide variety of tissues and acts in an autocrine or paracrine fashion. Parathyroid hormone-related protein and parathyroid hormone bind to and activate the same G-protein-coupled receptor. Here we present the structure of the biologically active NH2-terminal domain of human parathyroid hormone-related protein(1-34) in near-physiological solution in the absence of crowding reagents as determined by two-dimensional proton magnetic resonance spectroscopy. An improved strategy for structure calculation revealed the presence of two helices, His-5-Leu-8 and Gln-16-Leu-27, connected by a flexible linker. The parathyroid hormone-related protein(1-34) structure and the structure of human parathyroid hormone(1-37) as well as human parathyroid hormone(1-34) are highly similar, except for the well defined turn, His-14-Ser-17, present in parathyroid hormone. Thus, the similarity of the binding affinities of parathyroid hormone and parathyroid hormone-related protein to their common receptor may be based on their structural similarity.
甲状旁腺激素相关蛋白在恶性肿瘤体液性高钙血症的发病机制中起主要作用。在正常生理条件下，甲状旁腺激素相关蛋白在多种组织中产生，并以自分泌或旁分泌方式发挥作用。甲状旁腺激素相关蛋白和甲状旁腺激素结合并激活相同的G蛋白偶联受体。在此，我们通过二维质子磁共振波谱法确定了在不存在拥挤试剂的近生理溶液中，人甲状旁腺激素相关蛋白（1-34）具有生物活性的NH2末端结构域的结构。一种改进的结构计算策略揭示了存在两个螺旋，即His-5-Leu-8和Gln-16-Leu-27，它们由一个柔性接头连接。甲状旁腺激素相关蛋白（1-34）的结构与人甲状旁腺激素（1-37）以及人甲状旁腺激素（1-34）的结构高度相似，除了甲状旁腺激素中存在明确的转角His-14-Ser-17。因此，甲状旁腺激素和甲状旁腺激素相关蛋白与其共同受体的结合亲和力相似性可能基于它们的结构相似性。
