Widom Lab
June, 2009

From DNA sequence to transcriptional behaviour: a quantitative approach

Eran Segal and Jonathan Widom

Abstract: Complex transcriptional behaviours are encoded in the DNA sequences of gene regulatory regions. Advances in our understanding of these behaviours have been recently gained through quantitative models that describe how molecules such as transcription factors and nucleosomes interact with genomic sequences. An emerging view is that every regulatory sequence is associated with a unique binding affinity landscape for each molecule and, consequently, with a unique set of molecule-binding configurations and transcriptional outputs. We present a quantitative framework based on existing methods that unifies these ideas. This framework explains many experimental observations regarding the binding patterns of factors and nucleosomes and the dynamics of transcriptional activation. It can also be used to model more complex phenomena such as transcriptional noise and the evolution of transcriptional regulation.

Hoffman Lab
June, 2009

Electrostatic Redesign of the [Myoglobin,Cytochrome b5] Interface To Create a Well-Defined Docked Complex with Rapid Interprotein Electron Transfer

Peng Xiong, Judith M. Nocek, Amanda K. K. Griffin, Jingyun Wang, and Brian M. Hoffman

Find the text online here http://pubs.acs.org/doi/full/10.1021/ja902131d?cookieSet=1

Matouschek Lab
January, 2008

Substrate selection by the proteasome during degradation of protein complexes

The proteasome controls the turnover of many cellular proteins. Two structural features are typically required for proteins to be degraded: covalently attached ubiquitin polypeptides that allow binding to the proteasome and an unstructured region in the targeted protein that initiates proteolysis. Here, we have tested the degradation of model proteins to further explore how the proteasome selects its substrates. Using purified yeast proteasome and mammalian proteasome in cell lysate, we have demonstrated that the two structural features can act in trans when separated onto different proteins in a multisubunit complex. In such complexes, the location of the unstructured initiation site and its chemical properties determine which subunit is degraded. Thus, our findings reveal the molecular basis of subunit specificity in the degradation of protein complexes. In addition, our data provide a plausible explanation for how adaptor proteins can bind to otherwise stable proteins and target them for degradation.

Marko and Mondragon Groups
November, 2007

Topoisomerases are enzymes that remove topological constraints in double-stranded DNA introduced by processes such as replication, recombination and transcription.  The mechanism of action of Topoisomerase V, a new topoisomerase unrelated to other topoisomerases, has remained unknown.  The Mondragon and Marko groups now show via single-molecule experiments that Topoisomerase V employs a similar mechanism as type IB topoisomerases, but using a completely different structural framework.

The kinesin-1 motor protein is regulated by a direct interaction of its head and tail

The motor protein kinesin-1 has a regulatory tail domain that can simultaneously contact the enzymatically critical Switch I region of its motile head domains and the microtubule, according to an 8 Å cryo-EM reconstruction obtained by Dietrich et al. (Rice lab).  These interactions suggest a mechanism for tail-mediated regulation of kinesin-1's ATPase activity and raise the possibility of a paused state of kinesin-1 on microtubules.