Atomic structure of the SAGA complex and it's interaction with TBP.

Fiche publication


Date publication

février 2021

Journal

Comptes rendus biologies

Auteurs

Membres identifiés du Cancéropôle Est :
Dr SCHULTZ Patrick, Dr BEN SHEM Adam


Tous les auteurs :
Papai G, Frechard A, Kolesnikova O, Crucifix C, Schultz P, Ben-Shem A

Résumé

The transcription of eukaryotic protein genes is controlled by a plethora of proteins which act together in multi-component complexes to facilitate the DNA dependent RNA polymerase II (Pol II) enzyme to bind to the transcription start site and to generate messenger RNA from the gene's coding sequence. The protein that guides the transcription machinery to the exact transcription start site is called TATA-box Binding Protein, or TBP. TBP is part of two large protein complexes involved in Pol II transcription, TFIID and SAGA. The two complexes share several subunits implicated in the interaction with TBP and contain proteins with structural elements highly homologous to nucleosomal histones. Despite the intensive study of transcription initiation, the mode of interaction of TBP with these complexes and its release upon DNA binding was elusive. In this study we demonstrate the quasi-atomic model of SAGA in complex with TBP. The structure reveals the intricate network of interactions that coordinate the different functional domains of SAGA and resolves a deformed octamer of histone-fold domains at the core of SAGA. This deformed octamer is precisely tuned to establish a peripheral site for TBP binding, where it is protected by steric hindrance against the binding of spurious DNA. Complementary biochemical analysis points to a mechanism for TBP delivery and release from SAGA that requires the general transcription factor TFIIA and whose efficiency correlates with the affinity of DNA to TBP.As the TBP binding machinery is highly similar in TFIID and SAGA, we demonstrated a universal mechanism of how TBP is delivered to gene promoters during transcription initiation.

Mots clés

ARN messager, Genes, SGA, TBP, Transcription

Référence

C R Biol. 2021 Feb 4;343(3):247-255