کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5371555 1503953 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Binding specificity of the ectodomain of the parathyroid hormone receptor
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
Binding specificity of the ectodomain of the parathyroid hormone receptor
چکیده انگلیسی

The parathyroid hormone (PTH)1 receptor is a member of the class B G protein-coupled receptor (GPCR) family and regulates bone and mineral metabolism of vertebrates. A truncated highly active parathyroid hormone fragment PTH (1-34) exerts stimulatory effects on the receptor and is used for treatment of osteoporosis. To study the interacting amino acids of the natural peptide ligand PTH (1-84) with the ectodomain of its receptor we used peptide micro arrays on solid cellulose membranes. The amino acids Arg20 and Trp23 within the identified core binding stretch PTH (20-26) were found to be most important for affinity to the ectodomain of PTH1R. Isothermal titration calorimetry and NMR spectroscopy allowed peptide binding studies in solution and verified peptide positions required for high affinity. With this combination of biochemical and biophysical methods we extend former findings on this essential interaction and can now provide a strategy to screen for optimized therapeutic peptides.

Graphical AbstractResearch Highlights► Pin point GPCR ECD-binding competent stretch of parathyroid hormone PTH (1-84). ► Narrow this stretch down to a core peptide region: PTH (20-26). ► Identify single residues crucial for binding: Arg20, Trp23. ► Determine binding affinities of peptide variants in solution by ITC. ► Measure dynamic interaction in the PTH-nPTH1R complex by NMR at residue resolution.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biophysical Chemistry - Volume 154, Issues 2–3, March 2011, Pages 66-72
نویسندگان
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