Ternary complex between placental lactogen and the extracellular domain of the prolactin receptor.
The structure of the ternary complex between ovine placental lactogen (oPL) and the extracellular domain (ECD) of the rat prolactin receptor (rPRLR) reveals that two rPRLR ECDs bind to opposite sides of oPL with pseudo two-fold symmetry. The two oPL receptor binding sites differ significantly in their topography and electrostatic character. These binding interfaces also involve different hydrogen bonding and hydrophobic packing patterns compared to the structurally related human growth hormone (hGH)-receptor complexes. Additionally, the receptor-receptor interactions are different from those of the hGH-receptor complex. The conformational adaptability of prolactin and growth hormone receptors is evidenced by the changes in local conformations of the receptor binding loops and more global changes induced by shifts in the angular relationships between the N- and C-terminal domains, which allow the receptor to bind to the two topographically distinct sites of oPL.
Elkins
P A
PA
Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Christinger
H W
HW
Sandowski
Y
Y
Sakal
E
E
Gertler
A
A
de Vos
A M
AM
Kossiakoff
A A
AA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D019382:Human Growth Hormone / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010928:Placental Lactogen / Q000737:chemistry* / Q000378:metabolism*; D011388:Prolactin / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011981:Receptors, Prolactin / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D012756:Sheep; D012997:Solvents; D055672:Static Electricity; D013379:Substrate Specificity
D008565:Membrane Proteins; D011981:Receptors, Prolactin; D012997:Solvents; C405010:delta-hGHR; D019382:Human Growth Hormone; D011388:Prolactin; D010928:Placental Lactogen