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).

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

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.