In molecular biology, the OB-fold (oligonucleotide/oligosaccharide-binding fold) is a small
protein structural motif observed in different proteins that bind
oligonucleotides
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small fragments of nucleic aci ...
or
oligosaccharides
An oligosaccharide (; ) is a saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition and cell adhesion.
They are normally presen ...
. It was originally identified in 1993 in four unrelated proteins:
staphylococcal nuclease, anticodon binding domain of aspartyl-tRNA synthetase, and the B-subunits of heat-labile enterotoxin and verotoxin-1.
Since then it has been found in multiple proteins many of which are involved in genome stability. This fold is often described as a Greek key motif.
Structure
The OB-fold consists of a five-stranded
β-sheet
The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...
coiled to form a closed
β-barrel
In protein structures, a beta barrel (β barrel) is a beta sheet (β sheet) composed of Protein tandem repeats, tandem repeats that twists and coils to form a closed toroidal structure in which the first strand is bonded to the last strand (hydrog ...
, capped by an
α-helix
An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix).
The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...
located at one end and a binding cleft at the other. The α-helix packs against the bottom layer of residues, roughly perpendicular to the barrel axis. The β-sheet structure protrudes beyond this layer and packs around the sides of the helix. The binding specificities of each OB-fold depend on the different length, sequence, and conformation of the loops connecting the β-strands.
Structural determinants
OB-fold domains have several key structural determinants. These common features arise from physical principles governing
protein structure
Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, which are the monomers of the polymer. A single amino acid ...
rather than from
sequence homology
Sequence homology is the homology (biology), biological homology between DNA sequence, DNA, RNA sequence, RNA, or Protein primary structure, protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments ...
.
* β-sheet structure:
The closed β-sheet has specific parameters that determine
geometrical features like mean radius and average angle between strand directions and barrel axis.
* β-bulges:
Most structures have a common β-bulge in the first strand. β-bulges provide small increases in barrel radius and required coiling of β-strands.
* Interior residue packing:
The interior of the closed β-sheet has a regular three-layer structure of residues, with each β-strand contributing one residue to each layer.
* β-barrel deformation:
Many β-barrels are similarly flattened, with an elliptical cross-section.
* Barrel-helix interface:
A cavity on the barrel axis is filled by a large
hydrophobic
In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, thu ...
residue from the helix.
* Binding site location:
In some proteins, the
binding sites
In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...
are located on the side surface of the β-barrel where three loops come together, in such a way they are partially wrapped by the binding partner. In others, the binding cleft at the side of the barrel opposite to the helix functions as binding site.
Function
OB-folds are versatile
binding domains that can interact with
single-stranded DNA (ssDNA),
double-stranded DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of ...
(dsDNA),
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
,
proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
,
phospholipids
Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...
and
oligosaccharides
An oligosaccharide (; ) is a saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition and cell adhesion.
They are normally presen ...
. In genome guardian proteins, OB-folds play crucial roles in DNA binding and recognition,
protein-protein interactions and
catalytic
Catalysis () is the increase in reaction rate, rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst ...
functions in multi-subunit complexes.
Examples of proteins containing this domain
*
Single-stranded DNA binding protein (SSB)
*
Replication Protein A
Replication protein A (RPA) is the major protein that binds to single-stranded DNA (ssDNA) in eukaryotic cells. In vitro, RPA shows a much higher affinity for ssDNA than RNA or double-stranded DNA. RPA is required in replication, recombination ...
(RPA)
* RecG helicase
*
RuvA (part of the Holliday junction branch migration complex)
*
Minichromosome maintenance (MCM) proteins
* DNA ligase III
* RecO (recombination mediator)
Relationship to SH3 domains
OB-folds are structurally similar to
Src homology 3 (SH3) domains, with their β-strands superimposing with less than 2 Å difference. This structural similarity is important for understanding OB-fold function and regulation, as SH3 domains bind to PXXP-containing ligands in a pocket similar to the ssDNA binding pocket of many OB-folds.
Evolution and distribution
The OB-fold may represent a stable folding motif that appeared early in
protein evolution
Molecular evolution describes how inherited DNA and/or RNA change over evolutionary time, and the consequences of this for proteins and other components of cells and organisms. Molecular evolution is the basis of phylogenetic approaches to descr ...
, with its wide occurrence due to its adaptability to different functions and sequences.
OB-fold proteins present great versatility, which likely contributed to the development and widespread adoption of the fold in genome guardian proteins. They can adopt various
oligomerisation states and quaternary structures, allowing for complex and dynamic interactions. The OB-fold has flexibility in binding to a variety of substrates through variations in loop sizes, compositions, and insertions, showing a modular nature. In some cases, it can provide
catalytic
Catalysis () is the increase in reaction rate, rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst ...
functions to multi-subunit complexes, expanding its utility beyond just binding. Its structural similarity to SH3 domains allows OB-folds to participate in
protein-protein interactions, enabling regulation and complex formation.
References
{{Reflist
External links
InterPro: Nucleic acid-binding, OB-fold (IPR012340)
Protein domains
Protein folds
Protein superfamilies