Common fold in helix-hairpin-helix proteins

被引:114
作者
Shao, XG
Grishin, NV
机构
[1] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA
关键词
D O I
10.1093/nar/28.14.2643
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
Helix-hairpin-helix (HhH) is a widespread motif involved in non-sequence-specific DNA binding. The majority of HhH motifs function as DNA-binding modules, however, some of them are used to mediate protein-protein interactions or have acquired enzymatic activity by incorporating catalytic residues (DNA glycosylases), From sequence and structural analysis of HhH-containing proteins we conclude that most HhH motifs are integrated as a part of a five-helical domain, termed (HhH)(2) domain here. It typically consists of two consecutive HhH motifs that are linked by a connector helix and displays pseudo-5-fold symmetry. (HhH)(2) domains show clear structural integrity and a conserved hydrophobic core composed of seven residues, one residue from each alpha-helix and each hairpin, and deserves recognition as a distinct protein fold. In addition to known HhH in the structures of RuvA, RadA, MutY and DNA-polymerases, we have detected new HhH motifs in sterile alpha motif and barrier-to-autointegration factor domains, the alpha-subunit of Escherichia coli RNA-polymerase, DNA-helicase PcrA and DNA glycosylases, Statistically significant sequence similarity of HhH motifs and pronounced structural conservation argue for homology between (HhH)(2) domains in different protein families. Our analysis helps to clarify how non-symmetric protein motifs bind to the double helix of DNA through the formation of a pseudo-2-fold symmetric (HhH)(2) functional unit.
引用
收藏
页码:2643 / 2650
页数:8
相关论文
共 64 条
[1]   Protein data bank archives of three-dimensional macromolecular structures [J].
Abola, EE ;
Sussman, JL ;
Prilusky, J ;
Manning, NO .
MACROMOLECULAR CRYSTALLOGRAPHY, PT B, 1997, 277 :556-571
[2]   The N-terminal domain of the human Rad51 protein binds DNA: Structure and a DNA binding surface as revealed by NMR [J].
Aihara, H ;
Ito, Y ;
Kurumizaka, H ;
Yokoyama, S ;
Shibata, T .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 290 (02) :495-504
[3]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[4]   Iterated profile searches with PSI-BLAST - a tool for discovery in protein databases [J].
Altschul, SF ;
Koonin, EV .
TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (11) :444-447
[5]   Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches [J].
Aravind, L ;
Koonin, EV .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 287 (05) :1023-1040
[6]   DNA-binding proteins and evolution of transcription regulation in the archaea [J].
Aravind, L ;
Koonin, EV .
NUCLEIC ACIDS RESEARCH, 1999, 27 (23) :4658-4670
[7]   Pfam 3.1: 1313 multiple alignments and profile HMMs match the majority of proteins [J].
Bateman, A ;
Birney, E ;
Durbin, R ;
Eddy, SR ;
Finn, RD ;
Sonnhammer, ELL .
NUCLEIC ACIDS RESEARCH, 1999, 27 (01) :260-262
[8]   Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA [J].
Bruner, SD ;
Norman, DPG ;
Verdine, GL .
NATURE, 2000, 403 (6772) :859-866
[9]   Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration [J].
Cai, M ;
Huang, Y ;
Zheng, R ;
Wei, SQ ;
Ghirlando, R ;
Lee, MS ;
Craigie, R ;
Gronenborn, AM ;
Clore, GM .
NATURE STRUCTURAL BIOLOGY, 1998, 5 (10) :903-909
[10]   A helical arch allowing single-stranded DNA to thread through T5 5'-exonuclease [J].
Ceska, TA ;
Sayers, JR ;
Stier, G ;
Suck, D .
NATURE, 1996, 382 (6586) :90-93