Common features The overall structure of<unk>  is similar to that of other proteins in that it contains all of the common secondary structural elements (i.e., alpha helixes, beta pleated sheets, and random coils). Being a cytoplasmic protein requires that the protein be globular in structure, that is largely non-polar on the inside and polar on the outside, so as to be dissolved by water.<unk>  contains nine helices and eight anti-parallel beta pleated sheets, which combine to form several alpha/beta sandwiches. The 310 helices make up approximately 11% of the protein's amino acid residues, which is much higher than the average 4% in other proteins. Domain structure<unk>  consists of four structural domains: * a highly conserved N-terminal domain (NTD) of ~25 kDa * a "charged linker" region, that connects the N-terminus with the middle domain * a middle domain (MD) of ~40 kDa * a C-terminal domain (CTD) of ~12 kDa. Crystal structures are available for the N-terminal domain of yeast and human<unk> , for complexes of the N-terminus with inhibitors and nucleotides, and for the middle domain of yeast<unk> . Recently structures for full length<unk>  from E. coli (, ), yeast (, ), and the dog endoplasmic reticulum (, ) were elucidated.<unk>  forms homodimers where the contact sites are localized within the C-terminus in the open conformation of the dimer. The N-termini also come in contact in the closed conformation of the dimer. N-terminal domain The N-terminal domain shows homology not only among members of the<unk>  chaperone family but also to members of the ATPase/kinase GHKL (Gyrase,<unk> , Histidine Kinase, MutL) superfamily. A common binding pocket for ATP and the inhibitor geldanamycin is situated in the N-terminal domain. Amino acids that are directly involved in the interaction with ATP are Leu34, Asn37, Asp79, Asn92, Lys98, Gly121, and Phe124. In addition, Mg2+ and several water molecules form bridging electrostatic and hydrogen bonding interactions, respectively, between<unk>  and ATP. In addition, Glu33 is required for ATP hydrolysis. Middle domain The middle domain is divided into three regions: *a 3-layer α-β-α sandwich *a 3-turn α-helix and irregular loops *a 6-turn α-helix. The MD is also involved in client protein binding. For example, proteins known to interact this the<unk>  MD include PKB/Akt1, eNOS, Aha1, Hch1. Furthermore, substrate binding (e.g., by Aha1 and Hch1) to the MD is also known to increase the ATPase activity of<unk> . C-terminal domain The C-terminal domain possesses an alternative ATP-binding site, which becomes accessible when the N-terminal Bergerat pocket is occupied. At the very C-terminal end of the protein is the tetratricopeptide repeat (TPR) motif recognition site, the conserved MEEVD pentapeptide, that is responsible for the interaction with co-factors such as the immunophilins FKBP51 and FKBP52, the stress induced phosphoprotein 1 (Sti1/Hop), cyclophilin-40, PP5, Tom70, and many more.
Hsp90
HspE7
Bcl-xL
Bcl-2
Caspase-9
Mad2
IKK2
NLRP3