3ffd

From Proteopedia

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Template:STRUCTURE 3ffd

Contents 1 Structure of parathyroid hormone-related protein complexed to a neutralizing monoclonal antibody 2 Disease 3 Function 4 About this Structure 5 See Also 6 Reference

Structure of parathyroid hormone-related protein complexed to a neutralizing monoclonal antibody

Template:ABSTRACT PUBMED 19346515

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]

About this Structure

3ffd is a 3 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA.

See Also

• Monoclonal Antibody

Reference

• McKinstry WJ, Polekhina G, Diefenbach-Jagger H, Ho PW, Sato K, Onuma E, Gillespie MT, Martin TJ, Parker MW. Structural basis for antibody discrimination between two hormones that recognize the parathyroid hormone receptor. J Biol Chem. 2009 Jun 5;284(23):15557-63. doi: 10.1074/jbc.M900044200. Epub 2009 , Apr 4. PMID:19346515 doi:http://dx.doi.org/10.1074/jbc.M900044200

1. ↑ Klopocki E, Hennig BP, Dathe K, Koll R, de Ravel T, Baten E, Blom E, Gillerot Y, Weigel JF, Kruger G, Hiort O, Seemann P, Mundlos S. Deletion and point mutations of PTHLH cause brachydactyly type E. Am J Hum Genet. 2010 Mar 12;86(3):434-9. doi: 10.1016/j.ajhg.2010.01.023. Epub, 2010 Feb 18. PMID:20170896 doi:10.1016/j.ajhg.2010.01.023
2. ↑ Mula RV, Bhatia V, Falzon M. PTHrP promotes colon cancer cell migration and invasion in an integrin alpha6beta4-dependent manner through activation of Rac1. Cancer Lett. 2010 Dec 1;298(1):119-27. doi: 10.1016/j.canlet.2010.06.009. Epub, 2010 Jul 15. PMID:20637541 doi:10.1016/j.canlet.2010.06.009
3. ↑ Mula RV, Bhatia V, Falzon M. PTHrP promotes colon cancer cell migration and invasion in an integrin alpha6beta4-dependent manner through activation of Rac1. Cancer Lett. 2010 Dec 1;298(1):119-27. doi: 10.1016/j.canlet.2010.06.009. Epub, 2010 Jul 15. PMID:20637541 doi:10.1016/j.canlet.2010.06.009