3N06

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

3N06 の概要

• エントリーDOI: 10.2210/pdb3n06/pdb
• 関連するPDBエントリー: 3MZG 3N0P
• 分子名称: Prolactin, Prolactin receptor, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: ph dependence, hematopoietic cytokine, hormone-hormone receptor complex, hormone/hormone receptor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P01236; Membrane ; Single-pass type I membrane protein . Isoform 7: Secreted: P16471
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46275.08

構造登録者

Kulkarni, M.V.,Tettamanzi, M.C.,Murphy, J.W.,Keeler, C.,Myszka, D.G.,Chayen, N.E.,Lolis, E.J.,Hodsdon, M.E. (登録日: 2010-05-13, 公開日: 2010-09-29, 最終更新日: 2024-11-06)

主引用文献

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

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: 20889499
DOI: 10.1074/jbc.M110.172072

実験手法

X-RAY DIFFRACTION (2 Å)