1bzg
From Proteopedia
THE SOLUTION STRUCTURE OF HUMAN PARATHYROID HORMONE-RELATED PROTEIN (1-34) IN NEAR-PHYSIOLOGICAL SOLUTION, NMR, 30 STRUCTURES
Structural highlights
Disease[PTHR_HUMAN] Defects in PTHLH are the cause of brachydactyly type E2 (BDE2) [MIM:613382]. BDE2 is a form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. In brachydactyly type E2 variable combinations of metacarpals are involved, with shortening also of the first and third distal and the second and fifth middle phalanges.[1] Function[PTHR_HUMAN] Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Upregulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath (By similarity). Promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1-dependent manner through activation of Rac1.[2] Osteostatin is a potent inhibitor of osteoclastic bone resorption.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedParathyroid 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. The structure of human parathyroid hormone-related protein(1-34) in near-physiological solution.,Weidler M, Marx UC, Seidel G, Schafer W, Hoffmann E, Esswein A, Rosch P FEBS Lett. 1999 Feb 12;444(2-3):239-44. PMID:10050767[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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