Artigo prolactina

doi:10.1016/j.jmb.2005.06.042

J. Mol. Biol. (2005) 351, 810–823

Solution Structure of Human Prolactin
Kaare Teilum1, Jeffrey C. Hoch2, Vincent Goffin3,4, Sandrina Kinet4 Joseph A. Martial4 and Birthe B. Kragelund1*
Department of Protein Chemistry, Institute of Molecular Biology and Physiology, University of Copenhagen, Øster Farimagsgade 2A, DK-1353 Copenhagen K, Denmark Department of Molecular Microbial and Structural Biology, University of Connecticut Health Center Farmington CT 06030-3305 USA ´ Universite Paris Descartes ´ ´ Faculte de Medecine; INSERM U584, site Necker, 156 rue de Vaugirard Paris 75015, France Laboratoire de Biologie ´ ´ Moleculaire et de Genie ´ ´ Genetique, CBIG (Centre of Biomedical Integrative ´ Genoproteomics), Universite de ` ` Liege, B-4000 Liege, Belgium
4 3 2 1

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