Everything about Tertiary Structure totally explained
In
biochemistry and
chemistry, the
tertiary structure of a
protein or any other
macromolecule is its three-dimensional structure, as defined by the atomic coordinates.
Relationship to primary sequence
Tertiary structure is considered to be largely determined by the protein's
primary sequence, or the sequence of
amino acids of which it's composed. Efforts to predict tertiary structure from the primary sequence are known generally as
protein structure prediction. However, the environment in which a protein is synthesized and allowed to fold are significant determinants of its final shape and are usually not directly taken into account by current prediction methods. (Most such methods do rely on comparisons between the sequence to be predicted and sequences of known structure in the
Protein Data Bank and thus account for environment indirectly, assuming the target and template sequences share similar cellular contexts.) A large-scale experiment known as
CASP directly compares the performance of state-of-the-art prediction methods and is run once every two and a half years.
Determinants of tertiary structure
In
globular proteins, tertiary interactions are frequently stabilized by the sequestration of
hydrophobic amino acid residues in the protein core, from which water is excluded, and by the consequent enrichment of charged or hydrophilic residues on the protein's water-exposed surface. In
secreted proteins that don't spend time in the
cytoplasm,
disulfide bonds between
cysteine residues help to maintain the protein's tertiary structure. A variety of common and stable tertiary structures appear in a large number of proteins that are unrelated in both function and evolution - for example, many proteins are shaped like a
TIM barrel, named for the enzyme
triosephosphateisomerase. Another common structure is a highly stable dimeric
coiled coil structure composed of 2-7
alpha helices. Proteins are classified by the folds they represent in databases like
SCOP and
CATH.
Stability of native states
The most typical conformation of a protein in its
cellular environment is generally referred to as the
native state or
native conformation. It is commonly assumed that this most-populated state is also the most
thermodynamically stable conformation attainable for a given primary sequence; this is a reasonable first approximation but the claim assumes that the reaction isn't under
kinetic control - that is, that the time required for the protein to attain its native conformation after being
translated is small.
In the cell, a variety of protein
chaperones assist a newly synthesized polypeptide in attaining its native conformation. Some such proteins are highly specific in their function, such as
protein disulfide isomerase; others are very general and can be of assistance to most globular proteins - the prokaryotic
GroEL/
GroES system and the homologous eukaryotic
Heat shock proteins Hsp60/Hsp10 system fall into this category.
Some proteins explicitly take advantage of the fact that they can become kinetically trapped in a relatively high-energy conformation due to folding kinetics. Influenza
hemagglutinin, for example, is synthesized as a single polypeptide chain that acts as a kinetic trap. The "mature" activated protein is
proteolytically cleaved to form two polypeptide chains that are trapped in a high-energy conformation. Upon encountering a drop in
pH, the protein undergoes an energetically favorable conformational rearrangement that enables it to penetrate a host cell membrane.
Experimental determination
The majority of protein structures known to date have been solved with the experimental technique of X-ray
crystallography, which typically provides data of high resolution but provides no time-dependent information on the protein's conformational flexibility. A second common way of solving protein structures uses
NMR, which provides somewhat lower-resolution data in general and is limited to relatively small proteins, but can provide time-dependent information about the motion of a protein in solution. More is known about the tertiary structural features of soluble globular proteins than about
membrane proteins because the latter class is extremely difficult to study using these methods.
History
Since the tertiary structure of proteins is an important problem in biochemistry, and since structure determination is relatively difficult,
protein structure prediction has been a long-standing problem. The first predicted structure of
globular proteins was the
cyclol model of
Dorothy Wrinch, but this was quickly discounted as being inconsistent with experimental data. Modern methods are sometimes able to predict the tertiary structure
de novo to within 5
Å for small proteins (<120 residues) and under favorable conditions, for example, confident
secondary structure predictions.
Further Information
Get more info on 'Tertiary Structure'.
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