1rw5
From Proteopedia
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Solution structure of human prolactin
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Colorectal cancer OMIM:[604584], Hepatocellular cancer OMIM:[604584]
About this Structure
1RW5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of human prolactin., Teilum K, Hoch JC, Goffin V, Kinet S, Martial JA, Kragelund BB, J Mol Biol. 2005 Aug 26;351(4):810-23. PMID:16045928
Page seeded by OCA on Mon Nov 12 19:07:27 2007
