3NCC
A human Prolactin receptor antagonist in complex with the mutant extracellular domain H188A of the human prolactin receptor
Summary for 3NCC
Entry DOI | 10.2210/pdb3ncc/pdb |
Related | 3MZG 3N06 3N0P 3NCB 3NCE 3NCF |
Descriptor | Prolactin, Prolactin receptor, SODIUM ION, ... (6 entities in total) |
Functional Keywords | ph dependence, hematopoietic cytokine, hormone-hormone receptor complex, hormone/hormone receptor |
Biological source | Homo sapiens (human) More |
Cellular location | Secreted: P01236 Membrane ; Single-pass type I membrane protein . Isoform 7: Secreted: P16471 |
Total number of polymer chains | 2 |
Total formula weight | 46335.09 |
Authors | Kulkarni, M.V.,Tettamanzi, M.C.,Murphy, J.W.,Keeler, C.,Myszka, D.G.,Chayen, N.E.,Lolis, E.J.,Hodsdon, M.E. (deposition date: 2010-06-04, release date: 2010-09-29, Last modification date: 2023-09-06) |
Primary citation | Kulkarni, M.V.,Tettamanzi, M.C.,Murphy, J.W.,Keeler, C.,Myszka, D.G.,Chayen, N.E.,Lolis, E.J.,Hodsdon, M.E. Two Independent Histidines, One in Human Prolactin and One in Its Receptor, Are Critical for pH-dependent Receptor Recognition and Activation. J.Biol.Chem., 285:38524-38533, 2010 Cited by PubMed Abstract: 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 depends strongly on solution acidity over the physiologic range from pH 6 to pH 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. PubMed: 20889499DOI: 10.1074/jbc.M110.172072 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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