1RW5

Solution structure of human prolactin

1RW5 の概要

• エントリーDOI: 10.2210/pdb1rw5/pdb
• NMR情報: BMRB: 5599
• 分子名称: Prolactin (1 entity in total)
• 機能のキーワード: four helix bundle, cytokine, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01236
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22929.19

構造登録者

Teilum, K.,Hoch, J.,Martial, J.A.,Kragelund, B.B. (登録日: 2003-12-16, 公開日: 2005-02-22, 最終更新日: 2024-10-09)

主引用文献

Teilum, K.,Hoch, J.C.,Goffin, V.,Kinet, S.,Martial, J.A.,Kragelund, B.B.
Solution structure of human prolactin
J.Mol.Biol., 351:810-823, 2005

PubMed Abstract: We report the solution structure of human prolactin determined by NMR spectroscopy. Our result is a significant improvement over a previous structure in terms of number and distribution of distance restraints, regularity of secondary structure, and potential energy. More significantly, the structure is sufficiently different that it leads to different conclusions regarding the mechanism of receptor activation and initiation of signal transduction. Here, we compare the structure of unbound prolactin to structures of both the homologue ovine placental lactogen and growth hormone. The structures of unbound and receptor bound prolactin/placental lactogen are similar and no noteworthy structural changes occur upon receptor binding. The observation of enhanced binding at the second receptor site when the first site is occupied has been widely interpreted to indicate conformational change induced by binding the first receptor. However, our results indicate that this enhanced binding at the second site could be due to receptor-receptor interactions or some other free energy sources rather than conformational change in the hormone. Titration of human prolactin with the extracellular domain of the human prolactin receptor was followed by NMR, gel filtration and electrophoresis. Both binary and ternary hormone-receptor complexes are clearly detectable by gel filtration and electrophoresis. The binary complex is not observable by NMR, possibly due to a dynamic equilibrium in intermediate exchange within the complex. The ternary complex of one hormone molecule bound to two receptor molecules is on the contrary readily detectable by NMR. This is in stark contrast to the widely held view that the ternary prolactin-receptor complex is only transiently formed. Thus, our results lead to improved understanding of the prolactin-prolactin receptor interaction.

PubMed: 16045928
DOI: 10.1016/j.jmb.2005.06.042

実験手法

SOLUTION NMR