Structure and inhibition analysis of the mouse SAD-B C-terminal fragment.
The SAD (synapses of amphids defective) kinases, including SAD-A and SAD-B, play important roles in the regulation of neuronal development, cell cycle, and energy metabolism. Our recent study of mouse SAD-A identified a unique autoinhibitory sequence (AIS), which binds at the junction of the kinase domain (KD) and the ubiquitin-associated ... (UBA) domain and exerts autoregulation in cooperation with UBA. Here, we report the crystal structure of the mouse SAD-B C-terminal fragment including the AIS and the kinase-associated domain 1 (KA1) at 2.8 A resolution. The KA1 domain is structurally conserved, while the isolated AIS sequence is highly flexible and solvent-accessible. Our biochemical studies indicated that the SAD-B AIS exerts the same autoinhibitory role as that in SAD-A. We believe that the flexible isolated AIS sequence is readily available for interaction with KD-UBA and thus inhibits SAD-B activity.
Mesh Terms:
Amino Acid Sequence, Animals, Conserved Sequence, Mice, Models, Molecular, Peptide Fragments, Protein Domains, Protein Serine-Threonine Kinases
Amino Acid Sequence, Animals, Conserved Sequence, Mice, Models, Molecular, Peptide Fragments, Protein Domains, Protein Serine-Threonine Kinases
Biosci Biotechnol Biochem
Date: Oct. 01, 2016
PubMed ID: 27251228
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