Molecular structure of promoter-bound yeast TFIID

Olga Kolesnikova,Gabor Papai,Adam Ben-Shem,Patrick Schultz,Jie Luo,Jeff Ranish

doi:10.1038/s41467-018-07096-y

Abstract

Transcription preinitiation complex assembly on the promoters of protein encoding genes is nucleated in vivo by TFIID composed of the TATA-box Binding Protein (TBP) and 13 TBP-associate factors (Tafs) providing regulatory and chromatin binding functions. Here we present the cryo-electron microscopy structure of promoter-bound yeast TFIID at a resolution better than 5 Å, except for a flexible domain. We position the crystal structures of several subunits and, in combination with cross-linking studies, describe the quaternary organization of TFIID. The compact tri lobed architecture is stabilized by a topologically closed Taf5-Taf6 tetramer. We confirm the unique subunit stoichiometry prevailing in TFIID and uncover a hexameric arrangement of Tafs containing a histone fold domain in the Twin lobe.

Highlights

Transcription preinitiation complex assembly on the promoters of protein encoding genes is nucleated in vivo by TFIID composed of the TATA-box Binding Protein (TBP) and 13 TBPassociate factors (Tafs) providing regulatory and chromatin binding functions
A very unique subunit stoichiometry prevails in TFIID since a subset of six subunits are present in two copies (Taf5, 6, 9, 4, 12, 10), while the remaining seven Tafs are present as single copies
Genetic and biochemical evidence indicated that Taf[5], Taf[4], Taf[12], Taf[6] and Taf[9] are present as two copies in TFIID12 and a recombinant human core TFIID containing these 5 Tafs shows two-fold symmetry[20]

Summary

Introduction

Transcription preinitiation complex assembly on the promoters of protein encoding genes is nucleated in vivo by TFIID composed of the TATA-box Binding Protein (TBP) and 13 TBPassociate factors (Tafs) providing regulatory and chromatin binding functions. A striking feature of TFIID’s structural organization is that nine Tafs contain a stretch of amino acids with sequence homology to histones, including the histone fold (HF) domain involved in histone dimerization[14]. These homologies were confirmed by X-ray diffraction studies which revealed that drosophila Taf[9] and Taf[6] form a heterotetramer and interact through a characteristic histone fold[15] and that human Taf[11] and Taf1316, as well as Taf[4] and Taf1217 contain a HF used to form heterodimers. Genetic interactions of Taf[14] with Taf[2] were described and biochemically mapped to the Cterminus of Taf[223]

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Conclusion