The structure of the TFIIH p34 subunit reveals a von Willebrand factor A like fold.

Dominik R Schmitt,Jochen Kuper,Caroline Kisker,Agnes Elias

doi:10.1371/journal.pone.0102389

Abstract

RNA polymerase II dependent transcription and nucleotide excision repair are mediated by a multifaceted interplay of subunits within the general transcription factor II H (TFIIH). A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these vital cellular processes. The importance of this complex becomes further evident in the context of severe diseases like xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy, that arise from single point mutations in TFIIH subunits. Here we describe the structure of the p34 subunit of the TFIIH complex from the eukaryotic thermophilic fungus Chaetomium thermophilum. The structure revealed that p34 contains a von Willebrand Factor A (vWA) like domain, a fold which is generally known to be involved in protein-protein interactions. Within TFIIH p34 strongly interacts with p44, a positive regulator of the helicase XPD. Putative protein-protein interfaces are analyzed and possible binding sites for the p34-p44 interaction suggested.

Highlights

The transcription factor II H (TFIIH) complex is a multi-subunit protein assembly involved in transcription and DNA repair
Additional subunits like XPG and Tfb6 have been suggested [3,4] and ancillary interacting partners were identified [5], emphasizing the complexity of TFIIH and the high level of dynamics to participate in different processes
While both the TFIIH core and the CAK subcomplex are essential for RNA Polymerase II mediated transcription, the release of CAK from TFIIH promotes the excision of DNA lesions during the nucleotide excision repair (NER) pathway [6]

Summary

Introduction

The TFIIH complex is a multi-subunit protein assembly involved in transcription and DNA repair. A putative binding site for p44ct could be mapped onto the p34ct vWA domain, based on its electrostatic surface potential and previous studies.

Results

Conclusion