UCS Proteins: Chaperones for Myosin and Co-Chaperones for Hsp90 - The Networking of Chaperones by Co-chaperones - page 138

Fig. 7.3 Proposed models for myosin-specific chaperoning activities of UCS proteins Left panel :
TPR-containing UCS proteins, UNC-45, oligomerize to form scaffolds that serve as sites to recruit
multiprotein chaperone complexes, comprising of Hsp90, Hsp70 and UNC-45 itself, that simulta-
neously assist in myosin folding and myofilament formation. Right panel : TPR-less UCS proteins,
e.g. She4, act as adaptors that physically link two myosin heads to assist in folding them as well as
regulate their step size along actin filaments. (Note: this figure was adapted from Hellerschmied
and Clausen 2014 )
in the ATP- and actin-binding region, of a myosin V from yeast with a binding
affinity of approximately 1 ﾵM (Shi and Blobel 2010 ). Previous biochemical study
established that the TPR domain in UNC-45 binds Hsp90 peptide with a 10-fold
higher affinity than Hsp70 peptide (Barral et al. 2002 ), suggesting a more specific
interaction with the Hsp90 molecular chaperone. These biochemical and structural
studies have provided critical insights into the versatility of UCS proteins as myo-
sin-specific chaperones in general and perhaps molecular explanation of the evo-
lutionary requirement for TPR domain in UNC-45. In TPR-less homologs of UCS
proteins, typified by She4p, the neck region participates in dimerization such that
two L-shaped She4p molecules form a Z-shaped zigzag molecule. In this dimeric
form, She4p can act as adaptor that physically links two myosin heads to assist in
folding them as well as regulate their step size along actin filaments (Fig. 7.3 ; Shi
and Blobel 2010 ; Hellerschmied and Clausen 2014 ). In this model, Hsp90 can bind
in a TPR-independent manner to She4p-myosin complex to perform its chaperone
function. On the other hand, the chaperoning activity of UNC-45 appears to be more
sophisticated in higher eukaryotes in which highly organized myosin filaments