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Dongyan Tan, PhD - Harvard Medical School

Monday, March 09, 2015, 02:00pm - 03:00pm

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"Utilizing the Breakthroughs in Single-Particle Electron Microscopy to Study the Structures and Dynamics of Molecular
Machines"

Abstract:  Advances in detector hardware and image-processing software have revolutionized the field of
cryo-EM (electron microscopy). By combining these recent advancements we have determined the structure
of a AAA+(ATPases Associated with diverse cellular Activity) protein complex Pex1/Pex6 at 7.3 Å resolution
and built a pseudo-atomic model using the novel model building software RosettaCM. Pex1 and Pex6 alternate
in an hexameric double-ring in the model. The N-terminal ATPase domains are inactive, forming a symmetric
D1 ring, while the C-terminal domains are active, likely in different nucleotide states, and form an asymmetric
D2 ring. These results suggest how subunit activity is coordinated and indicate striking similarities between Pex1/Pex6
and p97.

The powerful and versatile single-particle EM technique is also very useful in obtaining structural information of
challenging biological samples. This is demonstrated through the second part of the talk, using the INO80-C
and SWR-C complexes as examples. These two enzymes are conserved members of a subfamily of
ATP-dependent chromatin-remodeling enzymes that play key roles in transcription and genome-maintenance pathways.
Our results demonstrate that these two remodeling enzymes have similar overall architectures.  Each enzyme
is characterized by a long, dynamic 'tail' domain and a compact 'head' that contains the Rvb1/Rvb2 subunits organized as hexameric rings. By combining the structural and functional data, our work implicates the Ies6/Arp5 module of INO80-C in regulating
conformational changes that couple nucleosome binding to remodeling.

Hosts: Mike Kilejdian and Stephen Burley

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Location 
Proteomics 120
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