Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Structure of the Drosophila melanogaster Flight Muscle Myosin Filament at 4.7 Å Resolution Reveals New Details of Non-myosin Proteins

Version 1 : Received: 3 September 2023 / Approved: 5 September 2023 / Online: 5 September 2023 (09:34:52 CEST)

A peer-reviewed article of this Preprint also exists.

Abbasi Yeganeh, F.; Rastegarpouyani, H.; Li, J.; Taylor, K.A. Structure of the Drosophila melanogaster Flight Muscle Myosin Filament at 4.7 Å Resolution Reveals New Details of Non-Myosin Proteins. Int. J. Mol. Sci. 2023, 24, 14936. Abbasi Yeganeh, F.; Rastegarpouyani, H.; Li, J.; Taylor, K.A. Structure of the Drosophila melanogaster Flight Muscle Myosin Filament at 4.7 Å Resolution Reveals New Details of Non-Myosin Proteins. Int. J. Mol. Sci. 2023, 24, 14936.

Abstract

Striated muscle thick filaments are composed of myosin II and several non- myosin proteins which define the filament length and modify its function. Myosin II has a globular N-terminal motor domain comprising its catalytic and actin-binding activities and a long α-helical, coiled-coil tail that forms the dense filament backbone. Myosin alone polymerizes into filaments of irregular length, but striated muscle thick filaments have defined lengths that with the thin filament define the sarcomere structure. The motor domain structure and function are well understood but the myosin filament backbone is not. Here we report a structure of the flight muscle thick filaments from Drosophila melanogaster at 4.7 Å resolution which eliminates previous ambiguities in the non-myosin densities. The full proximal S2 region is resolved as are the connecting densities between the Ig domains of stretchin-klp. The proteins, flightin and myofilin are resolved in sufficient detail to build an atomic model based on an AlphaFold prediction. Our results suggest how flightin and myofilin cooperate to define the structure of the thick filament and explains a key myosin mutation that affects flightin incorporation. Drosophila is a genetic model organism for which our results can define strategies for functional testing.

Keywords

cryo-electron microscopy; myosin; flightin; myofilin; stretchin; striated muscle; asynchronous flight muscle

Subject

Biology and Life Sciences, Life Sciences

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