 | This articleneeds additional citations forverification. Please helpimprove this article byadding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Protein tertiary structure" – news ·newspapers ·books ·scholar ·JSTOR(February 2025) (Learn how and when to remove this message) |
Protein tertiary structure is the three-dimensional shape of aprotein. The tertiary structure will have a singlepolypeptide chain "backbone" with one or moreprotein secondary structures, theprotein domains.Amino acidside 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 itsatomic 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 aquaternary structure.[3]
The science of the tertiary structure of proteins has progressed from one ofhypothesis to one of detailed definition. AlthoughEmil Fischer had suggested proteins were made ofpolypeptide chains and amino acid side chains, it wasDorothy Maud Wrinch who incorporatedgeometry into the prediction ofprotein structures. Wrinch demonstrated this with theCyclol model, the first prediction of the structure of aglobular protein.[4] Under favorable conditions, such as confident knowledge ofsecondary structure, contemporary methods are sometimes able to predict the tertiary structure of small proteins (<120 residues)de novo to within 5Å (0.5 nm).[citation needed][needs update]
A protein folded into itsnative state ornative conformation typically has a lowerGibbs free energy (a combination ofenthalpy andentropy) than the unfolded conformation. A protein will tend towards low-energy conformations, which will determine the protein's fold in thecellular environment. Because many similar conformations will have similar energies, protein structures aredynamic, fluctuating between these similar structures.
Globular proteins have a core ofhydrophobic amino acid residues and a surface region ofwater-exposed, charged,hydrophilic residues. This arrangement may stabilize interactions within the tertiary structure. For example, insecreted proteins, which are not bathed incytoplasm,disulfide bonds betweencysteine residues help to maintain the tertiary structure. There is a commonality of stable tertiary structures seen in proteins of diverse function and diverseevolution. For example, theTIM barrel, named for the enzymetriosephosphateisomerase, is a common tertiary structure as is the highly stable,dimeric,coiled coil structure. Hence, proteins may be classified by the structures they hold. Databases of proteins which use such a classification includeSCOP andCATH.
Foldingkinetics 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, theinfluenzahemagglutinin protein is a single polypeptide chain which when activated, isproteolytically cleaved to form two polypeptide chains. The two chains are held in a high-energy conformation. When the localpH drops, the protein undergoes an energetically favorable conformational rearrangement that enables it to penetrate the hostcell membrane.
Some tertiary protein structures may exist in long-lived states that are not the expected most stable state. For example, manyserpins (serine protease inhibitors) show thismetastability. They undergo aconformational change when a loop of the protein is cut by aprotease.[5][6][7]
It is commonly assumed that the native state of a protein is also the mostthermodynamically stable and that a protein will reach its native state, given itschemical kinetics, before it istranslated. Proteinchaperones within the cytoplasm of a cell assist a newly synthesised polypeptide to attain its native state. Some chaperone proteins are highly specific in their function, for example,protein disulfide isomerase; others are general in their function and may assist most globular proteins, for example, theprokaryoticGroEL/GroES system of proteins and thehomologouseukaryoticheat shock proteins (the Hsp60/Hsp10 system).
Prediction of protein tertiary structure relies on knowing the protein'sprimary structure and comparing the possible predicted tertiary structure with known tertiary structures inprotein data banks. This only takes into account the cytoplasmic environment present at the time ofprotein synthesis to the extent that a similar cytoplasmic environment may also have influenced the structure of the proteins recorded in the protein data bank.
The structure of a protein, such as anenzyme, may change upon binding of its natural ligands, for example acofactor. 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 locatedinside 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 andthe binding of specific molecules (biospecificity).
The knowledge of the tertiary structure of solubleglobular proteins is more advanced than that ofmembrane proteins because the former are easier to study with available technology.
X-ray crystallography is the most common tool used to determineprotein structure. It provides high resolution of the structure but it does not give information about protein'sconformational flexibility.
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 (cryo-EM) can give information about both a protein's tertiary and quaternary structure. It is particularly well-suited to large proteins andsymmetrical complexes ofprotein subunits.
Dual polarisation interferometry provides complementary information about surface captured proteins. It assists in determining structure and conformation changes over time.
TheFolding@home project at theUniversity of Pennsylvania is adistributed computing research effort which uses approximately 5petaFLOPS (≈10 x86 petaFLOPS) of available computing. It aims to find analgorithm which will consistently predict protein tertiary and quaternary structures given the protein's amino acid sequence and its cellular conditions.[9][10]
A list of software for protein tertiary structure prediction can be found atList of protein structure prediction software.
-en.svg){kind=link}