Structural highlights
2lfg is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.
Related: 1rw5, 3ew3, 3npz, 3d48, 3mzg
Activity: Glucokinase, with EC number 2.7.1.2
Publication Abstract from PubMed
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.
The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor.,Dagil R, Knudsen MJ, Olsen JG, O'Shea C, Franzmann M, Goffin V, Teilum K, Breinholt J, Kragelund BB Structure. 2012 Feb 8;20(2):270-82. PMID:22325776[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dagil R, Knudsen MJ, Olsen JG, O'Shea C, Franzmann M, Goffin V, Teilum K, Breinholt J, Kragelund BB. The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor. Structure. 2012 Feb 8;20(2):270-82. PMID:22325776 doi:http://dx.doi.org/10.1016/j.str.2011.12.010
