Structural characterization of the cysteine-rich domain of TFIIH p44 subunit.
In an effort to understand the structure function relationship of TFIIH, a transcription/repair factor, we focused our attention on the p44 subunit, which plays a central role in both mechanisms. The amino-terminal portion of p44 has been shown to be involved in the regulation of the XPD helicase activity; here we show that its carboxyl-terminal domain is essential for TFIIH transcription activity and that it binds three zinc atoms through two independent modules. The first contains a C4 zinc finger motif, whereas the second is characterized by a CX(2)CX(2-4)FCADCD motif, corresponding to interleaved zinc binding sites. The solution structure of this second module reveals an unexpected homology with the regulatory domain of protein kinase C and provides a framework to study its role at the molecular level.
Fribourg
S
S
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1, rue Laurent Fries, Boite Postale 163, 67404 Illkirch Cedex, France.
Kellenberger
E
E
Rogniaux
H
H
Poterszman
A
A
Van Dorsselaer
A
A
Thierry
J C
JC
Egly
J M
JM
Moras
D
D
Kieffer
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism; D016335:Zinc Fingers
D021122:Protein Subunits; D011994:Recombinant Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH; D006639:Histidine; D011493:Protein Kinase C; D004265:DNA Helicases; D015032:Zinc; D003545:Cysteine