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The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans.

<div class='caption-title'>Structure of UNC-45</div>
<div class='caption-title'>Interaction of UNC-45 with Its Partner Chaperones Hsp70 and Hsp90</div>
<div class='caption-title'>UNC-45 Interaction with Myosin</div>
Gazda L, Pokrzywa W, Hellerschmied D, Löwe T, Forné I, Mueller-Planitz F, Hoppe T, Clausen T
OpenAccess logo Cell 152 183-95 (2013)
Cited: 62 times
EuropePMC logo PMID: 23332754

Abstract

The UCS (UNC-45/CRO1/She4) chaperones play an evolutionarily conserved role in promoting myosin-dependent processes, including cytokinesis, endocytosis, RNA transport, and muscle development. To investigate the protein machinery orchestrating myosin folding and assembly, we performed a comprehensive analysis of Caenorhabditis elegans UNC-45. Our structural and biochemical data demonstrate that UNC-45 forms linear protein chains that offer multiple binding sites for cooperating chaperones and client proteins. Accordingly, Hsp70 and Hsp90, which bind to the TPR domain of UNC-45, could act in concert and with defined periodicity on captured myosin molecules. In vivo analyses reveal the elongated canyon of the UCS domain as a myosin-binding site and show that multimeric UNC-45 chains support organization of sarcomeric repeats. In fact, expression of transgenes blocking UNC-45 chain formation induces dominant-negative defects in the sarcomere structure and function of wild-type worms. Together, these findings uncover a filament assembly factor that directly couples myosin folding with myofilament formation.

Reviews - 4i2z mentioned but not cited (2)

  1. The UNC-45 myosin chaperone: from worms to flies to vertebrates. Lee CF, Melkani GC, Bernstein SI. Int Rev Cell Mol Biol 313 103-144 (2014)
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