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Seminar

Visualization of higher-order autophagy assemblies by cryo-EM

Dr Carsten SACHSE
Structural and Computational Biology Unit, EMBL, Heidelberg, Germany

Monday, June 18th 2018 - 2 p.m. - Conference room E1031, CBI
Hosted by Integrated structural Biology, Albert WEIXLBAUMER

Cryo-EM has become the method of choice to study the structures of large helical assemblies up to atomic resolution. I will present medium to high resolution oligomeric and polymeric cryo-EM structures that have advanced our understanding of the molecular mechanism of how cargo is recognized by the selective autophagy machinery. Throughout the talk, I will focus on the methodological advances that have led to the high-resolution structure elucidation [1]. These developments have taken us to address more general problems of improving cryo-EM map interpretation by local sharpening [2]. We show that autophagy receptor p62/SQSTM-1 assembles into flexible helical filaments and provides insights into the molecular basis of polymer formation [3]. EM based structure elucidation in vitro and in situ reveals large oligomeric and polymeric cargo receptor complexes giving rise to higher-order structures that constitute the scaffold for autophagosome formation [4]. The organization of small receptor proteins into helical assemblies constitutes a cellular mechanism for high selectivity in cargo recognition and a fundamental architecture that enables cargo encapsulation of various sizes from molecular to cellular scale.

 

 

References

 

[1]      S. A. Fromm and C. Sachse, “Cryo-EM Structure Determination Using Segmented Helical Image Reconstruction.,” Meth Enzymol, vol. 579, pp. 307–328, 2016.

[2]      A. J. Jakobi, M. Wilmanns, and C. Sachse, “Model-based local density sharpening of cryo-EM maps.,” eLife, vol. 6, p. 213, Oct. 2017.

[3]      R. Ciuffa, T. Lamark, A. K. Tarafder, A. Guesdon, S. Rybina, W. J. H. Hagen, T. Johansen, and C. Sachse, “The selective autophagy receptor p62 forms a flexible filamentous helical scaffold.,” Cell Rep, vol. 11, no. 5, pp. 748–758, May 2015.

[4]      C. Bertipaglia, S. Schneider, A. J. Jakobi, A. K. Tarafder, Y. S. Bykov, A. Picco, W. Kukulski, J. Kosinski, W. J. Hagen, A. C. Ravichandran, M. Wilmanns, M. Kaksonen, J. A. Briggs, and C. Sachse, “Higher-order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle.,” EMBO Rep, vol. 17, no. 7, pp. 1044–1060, Jul. 2016.

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