FC0003
Heat shock protein 90 TRP  -  Protein phosphatase 5 (Ppp5)

Biological function
Hsp90 is an essential molecular chaperone that is responsible for the activation or maturation of many key proteins of signal transduction pathways, including steroid hormone receptors, helix-loop-helix transcription factors, and tyrosine/threonine and serine/threonine kinases.

Structural evidence
Protein phosphatase 5 (Ppp5) binds to Hsp90 chaperone via a tetratricopeptide (TRP) repeat. The bound peptide exchanges between two distinct conformations. Two Glu residues anchor the peptide to the TPR domain at two distinct locations through ionic contacts (i.e. a two-carboxylate clamp), whereas the flanking region interchanges between two conformations of alternate hydrogen bonding patterns on the micro- to millisecond time scale.

Biochemical evidence
Ppp5 clamp is dynamic, although the affinity to Hsp90 is high (50 nM).

Structure/Mechanism
The Hsp90 binding site is close to the autoinhibitory surface of Ppp5, which is a possible allosteric mechanism for the relief of autoinhibition.

Mechanism category
flexibility/entropy modulation

Significance
Changes in binding site or peptide dynamics could make a significant contribution to affinity, as could changes in populations of multiple transient hydrogen bonds or to the average of long-range electrostatic interactions.