DNA binding proteins

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A DNA binding protein is a protein that binds to DNA .

properties

DNA-binding proteins are found in all living things and DNA viruses . They have at least one protein domain that can bind to DNA . The bond can be made to various functional groups . The backbone of the DNA consists of alternating phosphate and deoxyribose units. Due to the phosphate groups, the DNA is provided with negative charges in proportion to the chain length , to which protein domains with positively charged amino acids (e.g. lysine , arginine ) or protein domains with negatively charged amino acids with complexed cations (e.g. Mg 2+ or Zn 2+ complexes). Since the deoxyribose phosphate backbone repeats itself continuously, a protein that binds exclusively to the backbone cannot bind to a specific DNA sequence (no sequence specificity). Sequence-specific binding takes place through at least partial binding to a specific sequence of nucleobases ; the backbone can also be partly bound.

Sequence specificity

DNA-binding proteins without sequence specificity are e.g. B. the polymerases, helicases and generally proteins that slide along the DNA (e.g. with DNA clamps). Sequence-specific DNA-binding proteins are e.g. B. transcription factors that trigger gene expression at defined locations ( promoter ) . Due to the higher proportion of nucleobases in the surface, sequence-specific DNA-binding molecules tend to bind in the major groove of the DNA double helix. While some sequence-specific DNA-binding proteins prefer to bind single-stranded DNA (e.g. single-strand-binding protein), others bind double-stranded DNA (most of them) and a few also bind heteroduplexes of DNA and RNA (e.g. telomerase , reverse transcriptases , RNase H ).

Binding of single stranded DNA

Single-stranded DNA occurs permanently on the telomeres in eukaryotes and occurs temporarily in replication , transcription , recombination and DNA repair, e.g. B. the single-strand binding protein and some DNA repair enzymes.

Binding of double stranded DNA

Double-stranded DNA with complementary base pairing forms a double helix ( B-DNA ). This DNA double helix has a large and a small groove. The small groove has a smaller proportion of the nucleobases in the surface of the molecule, which is why it is less suitable for sequence-specific binding. Various DNA-binding molecules such as Lexitropsine , Netropsin , Distamycin , Hoechst 33342 , Pentamidine , DAPI or SYBR Green I bind to the minor groove of double-stranded DNA regardless of the sequence. Double-stranded binding proteins include histones or NS H-DNA-binding protein , high-mobility group , DNA polymerases , DNA-dependent RNA polymerases , helicases , topoisomerases , gyrases , ligases , polynucleotide - kinases , nucleases , some DNA repair enzymes . Sequence-specific dsDNA-binding proteins include transcription factors and some endonucleases . Prokaryotic transcription factors are mostly smaller than the gene expression products they control, while eukaryotic transcription factors are mostly larger than their controlled products and occasionally have multiple copies of a DNA-binding domain.

DNA-binding protein domains

Typical protein domains in dsDNA-binding proteins are the zinc finger domain , the AT hooks , the DNA clamp and the helix-turn-helix motif for DNA binding or the leucine zipper domain (bZIP) for dimerization . In the case of single-stranded DNA, the OB folding domain has been described , among other things .

ID

Methods for determining protein-DNA interactions (bound DNA sequence , DNA-binding proteins) are e.g. B. EMSA , DNase Footprinting Assay , ChIP , DamID , ChIP-on-Chip or ChIP-Seq .

Modeling

Different approaches to molecular modeling have been described. Algorithms for determining the bound DNA sequence have also been developed.

modification

In the course of a protein design , e.g. B. zinc finger proteins or TALENs can be designed. With the CRISPR / Cas method , corresponding DNA sequences can be bound using a complementary RNA sequence.

to form

Web links

Individual evidence

  1. ^ Travers, AA: DNA-protein interactions . Springer, London 1993, ISBN 978-0-412-25990-6 .
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  7. ^ TH Dickey, SE Altschuler, DS Wuttke: Single-stranded DNA-binding proteins: multiple domains for multiple functions. In: Structure (London, England: 1993). Volume 21, number 7, July 2013, pp. 1074-1084, doi : 10.1016 / j.str.2013.05.013 . PMID 23823326 . PMC 3816740 (free full text).
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  10. ↑ Zimmer C, Wähnert U: Nonintercalating DNA-binding ligands: specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material . In: Prog. Biophys. Mol. Biol . 47, No. 1, 1986, pp. 31-112. doi : 10.1016 / 0079-6107 (86) 90005-2 . PMID 2422697 .
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  14. ↑ Thomas J: HMG1 and 2: architectural DNA-binding proteins . In: Biochem Soc Trans . 29, No. Pt 4, 2001, pp. 395-401. doi : 10.1042 / BST0290395 . PMID 11497996 .
  15. ^ Grosschedl R, Giese K, Pagel J: HMG domain proteins: architectural elements in the assembly of nucleoprotein structures . In: Trends Genet . 10, No. 3, 1994, pp. 94-100. doi : 10.1016 / 0168-9525 (94) 90232-1 . PMID 8178371 .
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  21. ↑ teif VB, rib K .: Statistical-mechanical lattice models for protein-DNA binding in chromatin. . In: Journal of Physics: Condensed Matter . 2010. arxiv : 1004.5514 .
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  24. ↑ Created from PDB 1LMB
  25. ↑ Created from PDB 1RVA