6E16

Ternary structure of c-Myc-TBP-TAF1

Summary for 6E16

• Entry DOI: 10.2210/pdb6e16/pdb
• Descriptor: Transcription initiation factor TFIID subunit 1,Myc proto-oncogene protein,TATA-box-binding protein (2 entities in total)
• Functional Keywords: transcriptional regulation, carcinogenesis, dna binding protein
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 1
• Total formula weight: 28509.57

Authors

Wei, Y.,Dong, A.,Sunnerhagen, M.,Penn, L.,Tong, Y.,Edwards, A.M.,Arrowsmith, C.H.,Structural Genomics Consortium (SGC) (deposition date: 2018-07-09, release date: 2019-10-02, Last modification date: 2024-04-03)

Primary citation

Wei, Y.,Resetca, D.,Li, Z.,Johansson-Akhe, I.,Ahlner, A.,Helander, S.,Wallenhammar, A.,Morad, V.,Raught, B.,Wallner, B.,Kokubo, T.,Tong, Y.,Penn, L.Z.,Sunnerhagen, M.
Multiple direct interactions of TBP with the MYC oncoprotein.
Nat.Struct.Mol.Biol., 26:1035-1043, 2019

PubMed Abstract: Transcription factor c-MYC is a potent oncoprotein; however, the mechanism of transcriptional regulation via MYC-protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediating MYC-TBP interactions using structural, biochemical and cellular approaches. A 2.4 -Å resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1 (TAF1). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independently of TAF1. Modeling reveals that this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC-TBP interaction compromise MYC activity. We propose that MYC-TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly.

PubMed: 31686052
DOI: 10.1038/s41594-019-0321-z

Experimental method

X-RAY DIFFRACTION (2.4 Å)