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PuzzleFit Overview

The Puzzle-Fit project aims at developing new computational tools to integrate diverse experimental and in silico data to decipher the architecture of large multi-protein complexes. We focus in this project on the general transcription factor TFIID as a paradigm for a complex, multisubunit protein assembly composed of several interchangeable functional modules.

TFIID is composed of the TATA-box binding protein (TBP) and a group of 14 evolutionarily conserved proteins known as TBP-associated factors or TAFs. TFIID has been implicated in several human diseases by virtue of its binding properties with transcriptional activators or repressors or by the histone acetyl transferase (HAT) activity of its subunit TAF1.

TFIID constitutes a representative example of a macromolecular complex where a significant amount of structural, biophysical and functional information is already available, but where some crucial structural information on the spatial organization is still missing and hampers a full exploitation of the considerable amount of data already gathered. The main motivation of Puzzle-Fit is the observation that a large body of existing biochemical, genetic and biophysical data can be converted into spatial constraints that may help to solve the positional ambiguity.  Our aim is to integrate these diverse structural and biophysical data to elucidate the 3D architecture of TFIID at the highest possible resolution. We propose a multidisciplinary strategy including computational structural biology, bioinformatics, applied mathematics and experimental structural biology.

This multidisciplinary approach is implemented by cooperation between A. Dejaegere (advanced modelling), O. Lecompte (comparative genomics), N. Wicker (statistics and applied mathematics) and P. Schultz (cryo-EM and structure function studies of TFIID). The Puzzle-Fit project is funded by ANR (09-PIRI-0018-02).

Last Updated on Monday, 09 January 2012 16:27