A helix bundle is a small
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
fold composed of several
alpha helices
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 secondary structure of proteins. It is also the most extreme type of l ...
that are usually nearly parallel or antiparallel to each other.
Three-helix bundles
Three-helix bundles are among the smallest and fastest known cooperatively folding structural domains. The three-helix bundle in the
villin headpiece domain is only 36
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s long and is a common subject of study in
molecular dynamics
Molecular dynamics (MD) is a computer simulation method for analyzing the Motion (physics), physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamics ( ...
simulations because its
microsecond
A microsecond is a unit of time in the International System of Units (SI) equal to one millionth (0.000001 or 10−6 or ) of a second. Its symbol is μs, sometimes simplified to us when Unicode is not available.
A microsecond is to one second, ...
-scale folding time is within the timescales accessible to simulation. The 40-residue
HIV
The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
accessory protein has a very similar fold and has also been the subject of extensive study.
There is no general
sequence motif
In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''A ...
associated with three-helix bundles, so they cannot necessarily be
predicted from sequence alone. Three-helix bundles often occur in
actin-binding protein Actin-binding proteins (also known as ABPs) are proteins that bind to actin. This may mean ability to bind actin monomers, or polymers, or both.
Many actin-binding proteins, including α-actinin, β-spectrin, dystrophin, utrophin and fimbrin, do t ...
s and in
DNA-binding protein
DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, becau ...
s.
Four-helix bundles
Four-helix bundles typically consist of four helices packed in a
coiled-coil
A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a v ...
arrangement with a
steric
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivi ...
ally close-packed
hydrophobic core
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and to be excluded by water#Properties, water. The word hydrophobic literally means "water-fearing", and it describes the Segregation in m ...
in the center. Pairs of adjacent helices are often additionally stabilized by
salt bridges between charged amino acids. The helix axes typically are oriented about 20 degrees from their neighboring helices, a much shallower incline than in the larger helical structure of the
globin fold.
[Branden C, Tooze J. (1999). ''Introduction to Protein Structure'' 2nd ed. Garland Publishing: New York, NY.]
The specific topology of the helices is dependent on the protein – helices that are adjacent in sequence are often
antiparallel, although it is also possible to arrange antiparallel links between two pairs of parallel helices. Because
dimeric coiled-coils are themselves relatively stable, four-helix bundles can be
dimers of coiled-coil pairs, as in the
Rop protein. Four-helix bundle can have thermal stability more than 100 °C. Other important examples of four-helix bundles include
cytochrome
Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...
,
ferritin
Ferritin is a universal intracellular and extracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. ...
,
human growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
,
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
,
and
Lac repressor C-terminal. The four-helix bundle fold has proven an attractive target for de novo
protein design, with numerous de novo four-helix bundle proteins having been successfully designed by rational
and by combinatorial
methods. Although sequence is not conserved among four-helix bundles, sequence ''patterns'' tend to mirror those of coiled-coil structures in which every fourth and seventh residue is hydrophobic.
See also
*
Knobs into holes packing
References
External links
SCOP cytochrome c fold
{{Protein tertiary structure
Protein folds