Protein domain
Nature often brings several domains together to form multidomain and multifunctional proteins with a vast number of possibilities.
Domains can either serve as modules for building up large assemblies such as virus particles or muscle fibres, or can provide specific catalytic or binding sites as found in enzymes or regulatory proteins.
[13] The α/β-barrel is commonly called the TIM barrel named after triose phosphate isomerase, which was the first such structure to be solved.
[citation needed] The primary structure (string of amino acids) of a protein ultimately encodes its uniquely folded three-dimensional (3D) conformation.
[20] The most important factor governing the folding of a protein into 3D structure is the distribution of polar and non-polar side chains.
[21] Folding is driven by the burial of hydrophobic side chains into the interior of the molecule so to avoid contact with the aqueous environment.
For example, the β-hairpin motif consists of two adjacent antiparallel β-strands joined by a small loop.
The packing of the polypeptide is usually much tighter in the interior than the exterior of the domain producing a solid-like core and a fluid-like surface.
It also represents a model of evolution for functional adaptation by oligomerisation, e.g. oligomeric enzymes that have their active site at subunit interfaces.
Domains are the common material used by nature to generate new sequences; they can be thought of as genetically mobile units, referred to as 'modules'.
Often, the C and N termini of domains are close together in space, allowing them to easily be "slotted into" parent structures during the process of evolution.
[35] Four concrete examples of widespread protein modules are the following domains: SH2, immunoglobulin, fibronectin type 3 and the kringle.
Modular units frequently move about, within and between biological systems through mechanisms of genetic shuffling: The simplest multidomain organization seen in proteins is that of a single domain repeated in tandem.
[47] In the serine proteases, a gene duplication event has led to the formation of a two β-barrel domain enzyme.
[citation needed] A superdomain consists of two or more conserved domains of nominally independent origin, but subsequently inherited as a single structural/functional unit.
Anfinsen showed that the native state of a protein is thermodynamically stable, the conformation being at a global minimum of its free energy.
The Levinthal paradox states that if an averaged sized protein would sample all possible conformations before finding the one with the lowest energy, the whole process would take billions of years.
The forces that direct this search are likely to be a combination of local and global influences whose effects are felt at various stages of the reaction.
A funnel implies that for protein folding there is a decrease in energy and loss of entropy with increasing tertiary structure formation.
Protein domain dynamics play a key role in a multitude of molecular recognition and signaling processes.
The resultant dynamic modes cannot be generally predicted from static structures of either the entire protein or individual domains.
They can also be suggested by sampling in extensive molecular dynamics trajectories[62] and principal component analysis,[63] or they can be directly observed using spectra[64][65] measured by neutron spin echo spectroscopy.
[28][74][75][76][77] One of the first algorithms[70] used a Cα-Cα distance map together with a hierarchical clustering routine that considered proteins as several small segments, 10 residues in length.
[citation needed] The method by Sowdhamini and Blundell clusters secondary structures in a protein based on their Cα-Cα distances and identifies domains from the pattern in their dendrograms.
[66] As the procedure does not consider the protein as a continuous chain of amino acids there are no problems in treating discontinuous domains.
[citation needed] The method of Wodak and Janin[78] was based on the calculated interface areas between two chain segments repeatedly cleaved at various residue positions.
RigidFinder is a novel method for identification of protein rigid blocks (domains and loops) from two different conformations.
[81] The RIBFIND rigid bodies have been used to flexibly fit protein structures into cryo electron microscopy density maps.
[83] The latter allows users to optimally subdivide single-chain or multimeric proteins into quasi-rigid domains[62][83] based on the collective modes of fluctuation of the system.
By default the latter are calculated through an elastic network model;[84] alternatively pre-calculated essential dynamical spaces can be uploaded by the user.
