2LFG

Solution structure of the human prolactin receptor ecd domain d2

Summary for 2LFG

• Entry DOI: 10.2210/pdb2lfg/pdb
• Related: 1RW5 3D48 3EW3 3MZG 3NPZ
• NMR Information: BMRB: 17752
• Descriptor: Prolactin receptor (1 entity in total)
• Functional Keywords: extracellular domain, cytokine receptor, hormone receptor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein. Isoform 7: Secreted: P16471
• Total number of polymer chains: 1
• Total formula weight: 13343.34

Authors

Dagil, R.,Knudsen, M.J.,Kragelund, B.B.,O'Shea, C.,Teilum, K. (deposition date: 2011-06-30, release date: 2012-02-15, Last modification date: 2024-05-15)

Primary citation

Dagil, R.,Knudsen, M.J.,Olsen, J.G.,O'Shea, C.,Franzmann, M.,Goffin, V.,Teilum, K.,Breinholt, J.,Kragelund, B.B.
The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor
Structure, 20:270-282, 2012

PubMed Abstract: The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state. By contrast, in the hormone bound state, a Trp/Arg-ladder is formed. The conformational change is hormone-dependent and influences the receptor-receptor dimerization site 3. In the constitutively active, breast cancer-related receptor mutant PRLR(I146L), we observed a stabilization of the dimeric state and a change in the dynamics of the motif. Here we demonstrate a structural link between the WSXWS motif, hormone binding, and receptor dimerization and propose it as a general mechanism for class 1 receptor activation.

PubMed: 22325776
DOI: 10.1016/j.str.2011.12.010

Experimental method

SOLUTION NMR