8BRH
Co-crystal structure of She4 with Myo4 peptide
Summary for 8BRH
| Entry DOI | 10.2210/pdb8brh/pdb |
| Descriptor | KLLA0E16699p, Myo4 peptide (LYS-PHE-ILE-VAL-SER-HIS-TYR) (3 entities in total) |
| Functional Keywords | unc-45, ucs, myosin, chaperone |
| Biological source | Kluyveromyces lactis More |
| Total number of polymer chains | 2 |
| Total formula weight | 76751.93 |
| Authors | Arnese, R.,Gudino, R.,Meinhart, A.,Clausen, T. (deposition date: 2022-11-23, release date: 2024-06-05, Last modification date: 2024-08-14) |
| Primary citation | Vogel, A.,Arnese, R.,Gudino Carrillo, R.M.,Sehr, D.,Deszcz, L.,Bylicki, A.,Meinhart, A.,Clausen, T. UNC-45 assisted myosin folding depends on a conserved FX 3 HY motif implicated in Freeman Sheldon Syndrome. Nat Commun, 15:6272-6272, 2024 Cited by PubMed Abstract: Myosin motors are critical for diverse motility functions, ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control. We show that UNC-45 forms discrete complexes with folded and unfolded myosin, forwarding them to downstream chaperones and E3 ligases. Structural analysis of a minimal chaperone:substrate complex reveals that UNC-45 binds to a conserved FXHY motif in the myosin motor domain. Disrupting the observed interface by mutagenesis prevents myosin maturation leading to protein aggregation in vivo. We also show that a mutation in the FXHY motif linked to the Freeman Sheldon Syndrome impairs UNC-45 assisted folding, reducing the level of functional myosin. These findings demonstrate that a faulty myosin quality control is a critical yet unexplored cause of human myopathies. PubMed: 39054317DOI: 10.1038/s41467-024-50442-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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