UCS Proteins: Chaperones for Myosin and Co-Chaperones for Hsp90 - The Networking of Chaperones by Co-chaperones - page 131

Chapter 7
UCS Proteins: Chaperones for Myosin
and Co-Chaperones for Hsp90

Weiming Ni and Odutayo O. Odunuga

Abstract The UCS ( U NC-45/ C RO1/ S he4p) family of proteins has emerged as
chaperones that are specific for the folding, assembly and function of myosin. These
proteins participate in various important myosin-dependent cellular processes that
include myofibril organization and muscle functions, cell differentiation, cardiac
and skeletal muscle development, cytokinesis and endocytosis. Mutations in the
genes that code for UCS proteins cause serious defects in these actomyosin-based
processes. Homologs of UCS proteins can be broadly divided into (1) animal UCS
proteins, generally known as UNC-45 proteins, which contain an N-terminal tet-
ratricopeptide repeat (TPR) domain in addition to the canonical UCS domain, and
(2) fungal UCS proteins, which lack the TPR domain. Structurally, except for TPR
domain, both sub-classes of UCS proteins comprise of several irregular armadillo
(ARM) repeats that are divided into two-domain architecture: a combined central-
neck domain and a C-terminal UCS domain. Structural analyses suggest that UNC-
45 proteins form elongated oligomers that serve as scaffolds to recruit Hsp90 and/
or Hsp70 to form a multi-protein chaperoning complex that assists myosin heads to
fold and simultaneously organize them into myofibrils. Similarly, fungal UCS pro-
teins may dimerize to promote folding of non-muscle myosins as well as determine
their step size along actin filaments. These findings confirm UCS proteins as a new
class of myosin-specific chaperones and co-chaperones for Hsp90. This chapter
reviews the implications of the outcome of studies on these proteins in cellular pro-
cesses such as muscle formation, and disease states such as myopathies and cancer.

Keywords UCS ﾷ Myosin ﾷ TPR ﾷ Chaperones ﾷ Co-chaperones