3zhp is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
The MO25 scaffolding protein operates as critical regulator of a number of STE20 family protein kinases (e.g. MST and SPAK isoforms) as well as pseudokinases (e.g. STRAD isoforms that play a critical role in activating the LKB1 tumour suppressor). To better understand how MO25 interacts and stimulates the activity of STE20 protein kinases, we determined the crystal structure of MST3 catalytic domain (residues 19-289) in complex with full length MO25beta. The structure reveals an intricate web of interactions between MST3 and MO25beta that function to stabilise the kinase domain in a closed, active, conformation even in the absence of ATP or an ATP-mimetic inhibitor. The binding mode of MO25beta is reminiscent of the mechanism by which MO25alpha interacts with the pseudokinase STRADalpha. In particular we identified interface residues Tyr223 of MO25beta and Glu58 and Ile71 of MST3 that when mutated prevent activation of MST3 by MO25beta. These data provide molecular understanding of the mechanism by which MO25 isoforms regulates the activity of STE20 family protein kinases.
Structural insights into the activation of MST3 by MO25.,Mehellou Y, Alessi DR, Macartney TJ, Szklarz M, Knapp S, Elkins JM Biochem Biophys Res Commun. 2013 Feb 15;431(3):604-9. doi:, 10.1016/j.bbrc.2012.12.113. Epub 2013 Jan 4. PMID:23296203[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑ Mehellou Y, Alessi DR, Macartney TJ, Szklarz M, Knapp S, Elkins JM. Structural insights into the activation of MST3 by MO25. Biochem Biophys Res Commun. 2013 Feb 15;431(3):604-9. doi:, 10.1016/j.bbrc.2012.12.113. Epub 2013 Jan 4. PMID:23296203 doi:http://dx.doi.org/10.1016/j.bbrc.2012.12.113
