Lee Chi F, Melkani Girish C, Bernstein Sanford I
Department of Biology, San Diego State University, San Diego, CA, USA.
Int Rev Cell Mol Biol. 2014;313:103-44. doi: 10.1016/B978-0-12-800177-6.00004-9.
UNC-45 (uncoordinated mutant number 45) is a UCS (UNC-45, CRO1, She4p) domain protein that is critical for myosin stability and function. It likely aides in folding myosin during cellular differentiation and maintenance, and protects myosin from denaturation during stress. Invertebrates have a single unc-45 gene that is expressed in both muscle and nonmuscle tissues. Vertebrates possess one gene expressed in striated muscle (unc-45b) and another that is more generally expressed (unc-45a). Structurally, UNC-45 is composed of a series of α-helices connected by loops. It has an N-terminal tetratricopeptide repeat domain that binds to Hsp90 and a central domain composed of armadillo repeats. Its C-terminal UCS domain, which is also comprised of helical armadillo repeats, interacts with myosin. In this chapter, we present biochemical, structural, and genetic analyses of UNC-45 in Caenorhabditis elegans, Drosophila melanogaster, and various vertebrates. Further, we provide insights into UNC-45 functions, its potential mechanism of action, and its roles in human disease.
UNC-45（不协调突变体45）是一种UCS（UNC-45、CRO1、She4p）结构域蛋白，对肌球蛋白的稳定性和功能至关重要。它可能在细胞分化和维持过程中协助肌球蛋白折叠，并在应激期间保护肌球蛋白不发生变性。无脊椎动物有一个单一的unc-45基因，在肌肉和非肌肉组织中均有表达。脊椎动物有一个在横纹肌中表达的基因（unc-45b）和另一个广泛表达的基因（unc-45a）。在结构上，UNC-45由一系列通过环连接的α螺旋组成。它有一个与Hsp90结合的N端四肽重复结构域和一个由犰狳重复序列组成的中央结构域。其C端UCS结构域也由螺旋犰狳重复序列组成，与肌球蛋白相互作用。在本章中，我们展示了秀丽隐杆线虫、黑腹果蝇和各种脊椎动物中UNC-45的生化、结构和遗传分析。此外，我们深入探讨了UNC-45的功能、其潜在作用机制及其在人类疾病中的作用。
