The protein-binding potential of C2H2 zinc finger domains

被引:71
作者
Brayer, Kathryn J. [3 ]
Kulshreshtha, Sanjeev [1 ,2 ]
Segal, David J. [1 ,2 ]
机构
[1] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA
[2] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA
[3] Univ Arizona, Dept Pharmacol & Toxicol, Coll Pharm, Tucson, AZ 85721 USA
基金
美国国家科学基金会;
关键词
transcription factors; protein-DNA interactions; protein chemistry; structural biology; functional annotations;
D O I
10.1007/s12013-008-9007-6
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
There are over 10,000 C2H2-type zinc finger (ZF) domains distributed among more than 1,000 ZF proteins in the human genome. These domains are frequently observed to be involved in sequence-specific DNA binding, and uncharacterized domains are typically assumed to facilitate DNA interactions. However, some ZFs also facilitate binding to proteins or RNA. Over 100 Cys2-His2 (C2H2) ZF-protein interactions have been described. We initially attempted a bioinformatics analysis to identify sequence features that would predict a DNA- or protein-binding function. These efforts were complicated by several issues, including uncertainties about the full functional capabilities of the ZFs. We therefore applied an unbiased approach to directly examine the potential for ZFs to facilitate DNA or protein interactions. The human OLF-1/EBF associated zinc finger (OAZ) protein was used as a model. The human O/E-1-associated zinc finger protein (hOAZ) contains 30 ZFs in 6 clusters, some of which have been previously indicated in DNA or protein interactions. DNA binding was assessed using a target site selection (CAST) assay, and protein binding was assessed using a yeast two-hybrid assay. We observed that clusters known to bind DNA could facilitate specific protein interactions, but clusters known to bind protein did not facilitate specific DNA interactions. Our primary conclusion is that DNA binding is a more restricted function of ZFs, and that their potential for mediating protein interactions is likely greater. These results suggest that the role of C2H2 ZF domains in protein interactions has probably been underestimated. The implication of these findings for the prediction of ZF function is discussed.
引用
收藏
页码:9 / 19
页数:11
相关论文
共 55 条
[21]   ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A [J].
Ishiguro, Akira ;
Ideta, Maki ;
Mikoshiba, Katsuhiko ;
Chen, David J. ;
Aruga, Jun .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (13) :9983-9995
[22]   Principles of protein-protein interactions [J].
Jones, S ;
Thornton, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) :13-20
[23]   Small organic molecules that modulate gene transcription [J].
Jung, Dongju ;
Choi, Yongmun ;
Uesugi, Motonari .
DRUG DISCOVERY TODAY, 2006, 11 (9-10) :452-457
[24]   Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors [J].
Kelley, CM ;
Ikeda, T ;
Koipally, J ;
Avitahl, N ;
Wu, L ;
Georgopoulos, K ;
Morgan, BA .
CURRENT BIOLOGY, 1998, 8 (09) :508-515
[25]   Integr8 and Genome Reviews: integrated views of complete genomes and proteomes [J].
Kersey, P ;
Bower, L ;
Morris, L ;
Horne, A ;
Petryszak, R ;
Kanz, C ;
Kanapin, A ;
Das, U ;
Michoud, K ;
Phan, I ;
Gattiker, A ;
Kulikova, T ;
Faruque, N ;
Duggan, K ;
Mclaren, P ;
Reimhoiz, B ;
Duret, L ;
Penel, S ;
Reuter, I ;
Apweiler, R .
NUCLEIC ACIDS RESEARCH, 2005, 33 :D297-D302
[26]   Structural classification of zinc fingers [J].
Krishna, SS ;
Majumdar, I ;
Grishin, NV .
NUCLEIC ACIDS RESEARCH, 2003, 31 (02) :532-550
[27]   DNA-induced α-helix capping in conserved linker sequences is a determinant of binding affinity in Cys2-His2 zinc fingers [J].
Laity, JH ;
Dyson, HJ ;
Wright, PE .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 295 (04) :719-727
[28]   Induced fit and "lock and key" recognition of 5 S RNA by zinc fingers of transcription factor IIIA [J].
Lee, BM ;
Xu, J ;
Clarkson, BK ;
Martinez-Yamout, MA ;
Dyson, HJ ;
Case, DA ;
Gottesfeld, JM ;
Wright, PE .
JOURNAL OF MOLECULAR BIOLOGY, 2006, 357 (01) :275-291
[29]   EVIDENCE FOR PHYSICAL INTERACTION BETWEEN THE ZINC-FINGER TRANSCRIPTION FACTORS YY1 AND SP1 [J].
LEE, JS ;
GALVIN, KM ;
SHI, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (13) :6145-6149
[30]   3-DIMENSIONAL SOLUTION STRUCTURE OF A SINGLE ZINC FINGER DNA-BINDING DOMAIN [J].
LEE, MS ;
GIPPERT, GP ;
SOMAN, KV ;
CASE, DA ;
WRIGHT, PE .
SCIENCE, 1989, 245 (4918) :635-637