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SUMMARY:LMB Seminar: Cryo-ET reveals sarcomere structures at molecular res
 olution - Prof. Dr. Stefan Raunser\, Director\, Department of Structural B
 iochemistry\, Max Planck Institute of Molecular Physiology\, Dortmund
DTSTART:20221018T100000Z
DTEND:20221018T110000Z
UID:TALK182768@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Muscles underpin movement and heart function. Individual muscl
 e fibers can be very large syncytia of up to several centimeters in length
  and are comprised of the force-generating and load-bearing devices of mus
 cles called sarcomeres. Contraction and relaxation of sarcomeres relies on
  the sliding between two types of filaments - the thin filament (comprisin
 g mainly F-actin\, tropomyosin\, and troponin) and the thick myosin filame
 nt. In addition\, several other proteins are involved in the contraction m
 echanism and their mutational malfunction can lead to debilitating and eve
 n life-threatening diseases. In my presentation\, I will explain how we ma
 naged to obtain high-resolution structures of native sarcomeres using cryo
 -electron tomography (cryo-ET). Our cryo-ET reconstructions reveal molecul
 ar details of the three-dimensional organization and interaction of actin 
 and myosin in the A-band\, I-band and Z-disc and demonstrate that α-actin
 in cross-links antiparallel actin filaments by forming doublets with 6 nm 
 spacing. Structures of myosin\, tropomyosin\, actin\, and nebulin at up to
  4.5 Å further reveal two conformations of “double-headed” myosin\, w
 here the flexible orientation of the lever arm and light chains enable myo
 sin not only to interact with the same actin filament\, but also to split 
 between two actin filaments. The structures provide high-resolution detail
 s of the interaction between nebulin and actin\, demonstrating the stabili
 sing role of nebulin. Unexpectedly\, nebulin does not interact with myosin
  or tropomyosin\, but with a troponin-T linker through two potential bindi
 ng motifs on nebulin\, explaining its regulatory role. Our results provide
  unexpected insights into the fundamental organization of vertebrate skele
 tal muscle and serve as a strong foundation for future investigations of m
 uscle diseases.
LOCATION:In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoo
 m\, link: https://mrc-lmb-cam-ac-uk.zoom.us/j/96648790745?pwd=Tkx6OVpoY01i
 eTRMTFMzZ0QvWWR2UT09
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