3n06

A mutant human Prolactin receptor antagonist H27A in complex with the extracellular domain of the human prolactin receptor

spinqualitylabelsall models 3n06, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n06 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: CL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PRL_HUMAN Prolactin acts primarily on the mammary gland by promoting lactation. 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 PubMed Human prolactin (hPRL), a member of the family of hematopoietic cytokines, functions as both an endocrine hormone and autocrine/paracrine growth factor. We have previously demonstrated that recognition of the hPRL receptor (hPRLr) depends strongly on solution acidity over the physiologic range from pH 6 &- 8. The hPRL-receptor binding interface contains four histidines, whose protonation is hypothesized to regulate pH-dependent receptor recognition. Here, we systematically dissect its molecular origin by characterizing the consequences of His to Ala mutations on pH-dependent receptor-binding kinetics, site-specific histidine protonation, and high resolution structures of the intermolecular interface. Thermodynamic modeling of the pH dependence to receptor-binding affinity reveals large changes in site-specific protonation constants for a majority of interface histidines upon complexation. Removal of individual His imidazoles reduces these perturbations in protonation constants, which is most likely explained by the introduction of solvent-filled, buried cavities in the crystallographic structures without inducing significant conformational rearrangements. Two independent histidines, one in human prolactin and one in its receptor, are critical for pH dependent receptor recognition and activation.,Kulkarni MV, Tettamanzi MC, Murphy JW, Keeler C, Myszka DG, Chayen NE, Lolis EJ, Hodsdon ME J Biol Chem. 2010 Sep 30. PMID:20889499 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Prolactin Prolactin receptor

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