Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly

被引：32

作者：

Antonova, Simona, V ^{[1
]}

Haffke, Matthias ^{[2
,15
]}

Corradini, Eleonora ^{[3
,4
,5
]}

Mikuciunas, Mykolas ^{[1
]}

Low, Teck Y. ^{[3
,4
,5
,16
]}

Signor, Luca ^{[6
]}

van Es, Robert M. ^{[7
]}

Gupta, Kapil ^{[8
]}

Scheer, Elisabeth ^{[9
,10
,11
,12
]}

Vos, Harmjan R. ^{[7
]}

Tora, Laszlo ^{[9
,10
,11
,12
]}

Heck, Albert J. R. ^{[3
,4
,5
]}

Timmers, H. T. Marc ^{[1
,13
,14
]}

Berger, Imre ^{[8
]}

机构：

[1] Univ Med Ctr Utrecht, Mol Canc Res & Regenerat Med, Utrecht, Netherlands

[2] EMBL, Grenoble, France

[3] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote, Utrecht, Netherlands

[4] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands

[5] Univ Utrecht, Netherlands Prote Ctr, Utrecht, Netherlands

[6] Univ Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France

[7] Univ Med Ctr Utrecht, Ctr Mol Med, Mol Canc Res, Utrecht, Netherlands

[8] Univ Bristol, Bristol Synthet Biol Ctr BrisSynBio, Sch Biochem, Biomed Sci, Bristol, Avon, England

[9] Inst Genet & Biol Mol Cellulaire, Illkirch Graffenstaden, France

[10] CNRS, UMR 7104, Illkirch Graffenstaden, France

[11] INSERM, U964, Illkirch Graffenstaden, France

[12] Univ Strasbourg, Illkirch Graffenstaden, France

[13] Univ Freiburg, Med Ctr, Dept Urol, Freiburg, Germany

[14] Deutsch Krebsforschungszentrum DKFZ, Standort Freiburg, DKTK, Heidelberg, Germany

[15] Novartis Inst BioMed Res, Chem Biol & Therapeut, Basel, Switzerland

[16] Univ Kebangsaan Malaysia, UKM Med Mol Biol Inst UMBI, Kuala Lumpur, Malaysia

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2018年 / 25卷 / 12期

基金：

欧洲研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

AUTOMATED STRUCTURE SOLUTION; DENSITY MODIFICATION; COMPLEX; MODEL; CORE; EXPRESSION; INITIATION; MECHANISM; SAGA;

D O I：

10.1038/s41594-018-0156-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

TFIID is a cornerstone of eukaryotic gene regulation. Distinct TFIID complexes with unique subunit compositions exist and several TFIID subunits are shared with other complexes, thereby conveying precise cellular control of subunit allocation and functional assembly of this essential transcription factor. However, the molecular mechanisms that underlie the regulation of TFIID remain poorly understood. Here we use quantitative proteomics to examine TFIID submodules and assembly mechanisms in human cells. Structural and mutational analysis of the cytoplasmic TAF5-TAF6-TAF9 submodule identified novel interactions that are crucial for TFIID integrity and for allocation of TAF9 to TFIID or the Spt-Ada-Gcn5 acetyltransferase (SAGA) co-activator complex. We discover a key checkpoint function for the chaperonin CCT, which specifically associates with nascent TAF5 for subsequent handover to TAF6-TAF9 and ultimate holo-TFIID formation. Our findings illustrate at the molecular level how multisubunit complexes are generated within the cell via mechanisms that involve checkpoint decisions facilitated by a chaperone.

引用

页码：1119 / +

页数：11

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