Definition of protein kinase sequence motifs that trigger high affinity binding of Hsp90 and Cdc37.

摘要: Abstract Hsp90 cooperates with its co-chaperone Cdc37 to provide obligatory support numerous protein kinases involved in the regulation of cellular signal transduction pathways. In this report, crystal structure Src family tyrosine kinase Lck was used guide creation constructs determine features recognized by and “kinase-specific” Cdc37. Two parameters were assayed: ability extent which bound Cdc37, trigger salt-resistant high affinity complexes independent presence molybdate. Although interacted both N-terminal C-terminal lobes (NL CL, respectively) catalytic domains kinases, themselves not sufficient binding Hsp90. Only containing a complete N- or lobe part adjacent salt-stable The two minimum that contained α-C-helix β4- β5-strands NL through end CL α-E-helix amino acids cap helix. only minimally required Lck. results indicate activity is triggered interaction subdomain structures domains. Furthermore, adjoining loop connection β4-strand appear be primary determinants