Protein tertiary structure

Source: Wikipedia, the free encyclopedia.
This article is about tertiary structure in protein. For the article about tertiary structure in nucleic acid, see Nucleic acid tertiary structure.
Protein primary structureProtein secondary structureProtein tertiary structureProtein quaternary structure
The image above contains clickable links
The image above contains clickable links
PCNA as an example. (PDB: 1AXC
​)
Tertiary Structure of a Protein
The tertiary structure of a protein consists of the way a polypeptide is formed of a complex molecular shape. This is caused by R-group interactions such as ionic and hydrogen bonds, disulphide bridges, and hydrophobic & hydrophilic interactions.

Protein tertiary structure is the three-dimensional shape of a

polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the backbone may interact and bond in a number of ways. The interactions and bonds of side chains within a particular protein determine its tertiary structure. The protein tertiary structure is defined by its atomic coordinates. These coordinates may refer either to a protein domain or to the entire tertiary structure.[1][2] A number of these structures may bind to each other, forming a quaternary structure.[3]

History

The science of the tertiary structure of proteins has progressed from one of

secondary structure
predictions.

Determinants

Main article: Protein folding

Stability of native states

Thermostability

See also: Equilibrium unfolding

A protein folded into its

native conformation typically has a lower Gibbs free energy (a combination of enthalpy and entropy) than the unfolded conformation. A protein will tend towards low-energy conformations, which will determine the protein's fold in the cellular environment. Because many similar conformations will have similar energies, protein structures are dynamic
, fluctuating between these similar structures.

CATH
.

Kinetic traps

Folding kinetics may trap a protein in a high-energy conformation, i.e. a high-energy intermediate conformation blocks access to the lowest-energy conformation. The high-energy conformation may contribute to the function of the protein. For example, the influenza hemagglutinin protein is a single polypeptide chain which when activated, is proteolytically cleaved to form two polypeptide chains. The two chains are held in a high-energy conformation. When the local pH drops, the protein undergoes an energetically favorable conformational rearrangement that enables it to penetrate the host cell membrane.

Metastability

Some tertiary protein structures may exist in long-lived states that are not the expected most stable state. For example, many

serpins (serine protease inhibitors) show this metastability. They undergo a conformational change when a loop of the protein is cut by a protease.[5][6][7]

Chaperone proteins

It is commonly assumed that the native state of a protein is also the most

eukaryotic heat shock proteins
(the Hsp60/Hsp10 system).

Cytoplasmic environment

Prediction of protein tertiary structure relies on knowing the protein's

protein data banks. This only takes into account the cytoplasmic environment present at the time of protein synthesis
to the extent that a similar cytoplasmic environment may also have influenced the structure of the proteins recorded in the protein data bank.

Ligand binding

The structure of a protein, such as an enzyme, may change upon binding of its natural ligands, for example a cofactor. In this case, the structure of the protein bound to the ligand is known as holo structure, while the unbound protein has an apo structure.[8]

Structure stabilized by the formation of weak bonds between amino acid side chains - Determined by the folding of the polypeptide chain on itself (nonpolar residues are located inside the protein, while polar residues are mainly located outside) - Envelopment of the protein brings the protein closer and relates a-to located in distant regions of the sequence - Acquisition of the tertiary structure leads to the formation of pockets and sites suitable for the recognition and the binding of specific molecules (biospecificity).

Determination

The knowledge of the tertiary structure of soluble globular proteins is more advanced than that of membrane proteins because the former are easier to study with available technology.

X-ray crystallography

X-ray crystallography is the most common tool used to determine protein structure. It provides high resolution of the structure but it does not give information about protein's conformational flexibility.

NMR

Protein NMR
gives comparatively lower resolution of protein structure. It is limited to smaller proteins. However, it can provide information about conformational changes of a protein in solution.

Cryogenic electron microscopy

Cryogenic electron microscopy (cryo-EM) can give information about both a protein's tertiary and quaternary structure. It is particularly well-suited to large proteins and symmetrical complexes of protein subunits.

Dual polarisation interferometry

Dual polarisation interferometry
provides complementary information about surface captured proteins. It assists in determining structure and conformation changes over time.

Projects

Prediction algorithm

The

petaFLOPS (≈10 x86 petaFLOPS) of available computing. It aims to find an algorithm which will consistently predict protein tertiary and quaternary structures given the protein's amino acid sequence and its cellular conditions.[9][10][11]

A list of software for protein tertiary structure prediction can be found at List of protein structure prediction software.

Protein aggregation diseases

disease models. This is done by causing the disease in laboratory animals, for example, by administering a toxin, such as MPTP to cause Parkinson's disease, or through genetic manipulation.[12][13]
Protein structure prediction is a new way to create disease models, which may avoid the use of animals.[14]

Protein Tertiary Structure Retrieval Project (CoMOGrad)

Matching patterns in tertiary structure of a given protein to huge number of known protein tertiary structures and retrieve most similar ones in ranked order is in the heart of many research areas like function prediction of novel proteins, study of evolution, disease diagnosis, drug discovery, antibody design etc. The CoMOGrad project at BUET is a research effort to device an extremely fast and much precise method for protein tertiary structure retrieval and develop online tool based on research outcome.[15][16]

See also

References

  1. doi:10.1351/goldbook.T06282
  2. ^ Branden C. and Tooze J. "Introduction to Protein Structure" Garland Publishing, New York. 1990 and 1991.
  3. ISBN 0-8153-1701-8
  4. ISBN 0-19-991083-9
    , 9780199910830. Accessed at Google Books 8 December 2013.
  5. PMID 17079131
    .
  6. PMID 12475206
    .
  7. PMID 10669617
    .
  8. PMID 20066034
    .
  9. ^ "Folding@home." Stanford University. Accessed 18 December 2013.
  10. ^ "Folding@home – FAQ" Stanford University. Accessed 18 December 2013.
  11. ^ "Folding@home – Science." Stanford University.
  12. S2CID 1824912
    .
  13. ^ "Tp53 Knockout Rat". Cancer. Retrieved 2010-12-18.
  14. ^ "Feature – What is Folding and Why Does it Matter?". Archived from the original on December 12, 2013. Retrieved December 18, 2010.
  15. ^ "Comograd :: Protein Tertiary Matching".
  16. PMID 26293226
    .

External links
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