1bl1
From Proteopedia
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PTH RECEPTOR N-TERMINUS FRAGMENT, NMR, 1 STRUCTURE
Contents |
Overview
A 31 amino acid fragment of the extracellular N-terminus of the human, G-protein coupled receptor for parathyroid hormone (PTH1R) has been, structurally characterized by NMR and molecular dynamics simulations. The, fragment PTH1R[168-198] includes residues 173-189, shown by photoaffinity, cross-linking to be a contact domain with position 13 of parathyroid, hormone (PTH). The structure of PTH1R[168-198], determined in a micellar, solution of dodecylphosphocholine to mimic the membrane environment, consists of three alpha-helices, separated by a well-defined turn and a, flexible region. The topological orientation of PTH1R[168-198] was, determined from nitroxide-radical induced relaxation of NMR signals, utilizing 5- and 16-doxylstearic acid. The C-terminal helix (residues, 190-196), consisting of seven amino acids of the first transmembrane, domain, is very hydrophobic and embedded in the lipid core. This helix is, preceded by a well-defined turn, forming an approximate 90 degrees bend, placing the other helices (residues 169-176 and 180-189), both of which, are amphipathic, on the surface of the micelle. In this orientation, many, hydrophilic residues of the receptor, including Glu177, Arg179, Arg181, Glu182, Asp185, and Arg186, are projecting toward the solvent available to, form complementary Coulombic interactions with the polar residues of the, principal binding domain of the ligand (e.g., Arg25, Lys26, Lys27, Asp30, and His32). Given that the binding domain of PTH adopts an amphipathic, alpha-helix which lies on the membrane, we visualize ligand binding as a, two stage process involving a nonspecific hydrophobic interaction of, amphipathic helices with the membrane, followed by two-dimensional, diffusion leading to highly specific, ligand-receptor interaction.
Disease
Known diseases associated with this structure: Enchondromatosis, Ollier type OMIM:[168468], Metaphyseal chondrodysplasia, Murk Jansen type OMIM:[168468]
About this Structure
1BL1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Binding domain of human parathyroid hormone receptor: from conformation to function., Pellegrini M, Bisello A, Rosenblatt M, Chorev M, Mierke DF, Biochemistry. 1998 Sep 15;37(37):12737-43. PMID:9737850
Page seeded by OCA on Mon Nov 12 16:11:15 2007
