4I2Z

Crystal structure of the myosin chaperone UNC-45 from C.elegans in complex with a Hsp90 peptide

Summary for 4I2Z

• Entry DOI: 10.2210/pdb4i2z/pdb
• Related: 4I2W
• Descriptor: Protein UNC-45, Heat shock protein 90 (3 entities in total)
• Functional Keywords: chaperone, myosin folding, protein filaments, myofilament formation, tpr-peptide interaction, ucs domain containing protein, hsp70 and hsp90 co-chaperone, chaperone-protein binding complex, chaperone/protein binding
• Biological source: Caenorhabditis elegans (nematode); More
• Cellular location: Cytoplasm, perinuclear region: Q18688
• Total number of polymer chains: 2
• Total formula weight: 110109.28

Authors

Clausen, T.,Gazda, L.,Hellerschmied, D. (deposition date: 2012-11-23, release date: 2013-03-13, Last modification date: 2024-11-20)

Primary citation

Gazda, L.,Pokrzywa, W.,Hellerschmied, D.,Lowe, T.,Forne, I.,Mueller-Planitz, F.,Hoppe, T.,Clausen, T.
The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans.
Cell(Cambridge,Mass.), 152:183-195, 2013

PubMed 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.

PubMed: 23332754
DOI: 10.1016/j.cell.2012.12.025

Experimental method

X-RAY DIFFRACTION (2.9 Å)