Protein Assembly Lines

Dissection of myosin folding and assembly pathways

Muscle development and function rely on the correct assembly of contractile units called the sarcomeres. Their main components, thin (actin) and thick (myosin) filaments are organized in a precisely ordered, quasi-crystalline protein framework that mediates muscle contraction. Although the overall architecture of the sarcomere has been studied in detail, little is known about its complicated assembly process. In particular, the mechanism of myosin incorporation into thick filaments is poorly understood.

Given the great importance of myosin activity for life on earth, folding of myosin represents an equally important process. To this end, the myosin motor domain comprises a relatively complicated protein fold that requires the activity of several chaperones to reach its functional state. Moreover, the assembly of the myosin filament and its organization within the muscle sarcomere has to be coordinated - spatially and temporally - with the folding of the motor domain. So far, it has been shown that the folding of myosin involves the assistance of certain molecular chaperones including CCT, Hsp70 and Hsp90. In addition, UCS proteins, which are myosin-specific assembly factors with a characteristic UCS (UNC-45/Cro1/She4) domain, have been shown to be critical for myosin function; however, the exact mechanism of UCS proteins as well as their interactions with the general folding factors has not been determined so far.

In this project, we are interested in …

  • the folding and assembly of myosin and myofilaments.
  • the networking of chaperones during this process.
  • revealing general principles of putting multi-protein complexes together.

Projects in the lab

UCS proteins - as versatile myosin chaperones