4YNZ

Structure of the N-terminal domain of SAD

Summary for 4YNZ

• Entry DOI: 10.2210/pdb4ynz/pdb
• Related: 4YOM
• Descriptor: Serine/threonine-protein kinase BRSK2 (2 entities in total)
• Functional Keywords: kinase domain, uba domain, transferase
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : Q69Z98
• Total number of polymer chains: 2
• Total formula weight: 78825.55

Authors

Wu, J.X.,Wang, J.,Chen, L.,Wang, Z.X.,Wu, J.W. (deposition date: 2015-03-11, release date: 2015-12-16, Last modification date: 2023-11-08)

Primary citation

Wu, J.X.,Cheng, Y.S.,Wang, J.,Chen, L.,Ding, M.,Wu, J.W.
Structural insight into the mechanism of synergistic autoinhibition of SAD kinases
Nat Commun, 6:8953-8953, 2015

PubMed Abstract: The SAD/BRSK kinases participate in various important life processes, including neural development, cell cycle and energy metabolism. Like other members of the AMPK family, SAD contains an N-terminal kinase domain followed by the characteristic UBA and KA1 domains. Here we identify a unique autoinhibitory sequence (AIS) in SAD kinases, which exerts autoregulation in cooperation with UBA. Structural studies of mouse SAD-A revealed that UBA binds to the kinase domain in a distinct mode and, more importantly, AIS nestles specifically into the KD-UBA junction. The cooperative action of AIS and UBA results in an 'αC-out' inactive kinase, which is conserved across species and essential for presynaptic vesicle clustering in C. elegans. In addition, the AIS, along with the KA1 domain, is indispensable for phospholipid binding. Taken together, these data suggest a model for synergistic autoinhibition and membrane activation of SAD kinases.

PubMed: 26626945
DOI: 10.1038/ncomms9953

Experimental method

X-RAY DIFFRACTION (2 Å)