Protein tertiary structure: Difference between revisions
imported>Raihanur No edit summary |
imported>Preimage →History: Partially rv 10:56, 8 December 2013: (intended copyedit, but inadvertently changed meaning) + copyedit for clarity + tag with {{update inline}} |
||
| (One intermediate revision by one other user not shown) | |||
| Line 5: | Line 5: | ||
{{Protein structure}} | {{Protein structure}} | ||
[[File:Tertiary Structure of a Protein.svg|alt=Tertiary Structure of a Protein|frame|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.]] | [[File:Tertiary Structure of a Protein.svg|alt=Tertiary Structure of a Protein|frame|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 [[protein]]. The tertiary structure will have a single [[polypeptide]] chain "backbone" with one or more [[protein secondary structure]]s, the [[protein domain]]s. [[Amino acid]] [[side chain]]s 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 [[atom]]ic coordinates. These coordinates may refer either to a protein domain or to the entire tertiary structure.<ref>{{GoldBookRef|title=tertiary structure|file=T06282}}</ref><ref name="bran"> | '''Protein tertiary structure''' is the three-dimensional shape of a [[protein]]. The tertiary structure will have a single [[polypeptide]] chain "backbone" with one or more [[protein secondary structure]]s, the [[protein domain]]s. [[Amino acid]] [[side chain]]s 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 [[atom]]ic coordinates. These coordinates may refer either to a protein domain or to the entire tertiary structure.<ref>{{GoldBookRef|title=tertiary structure|file=T06282}}</ref><ref name="bran">{{cite book |last1=Brändén |first1=Carl-Ivar |last2=Tooze |first2=John |title=Introduction to protein structure |date=1999 |publisher=Garland Science |location=New York |isbn=978-0-8153-2305-1 |edition=2nd}}</ref> A number of these structures may bind to each other, forming a [[Protein quaternary structure|quaternary structure]].<ref name=kyte>{{cite book |last1=Kyte |first1=Jack |title=Structure in protein chemistry |date=1995 |publisher=Garland Pub |location=New York |isbn=0-8153-1701-8}}</ref> | ||
== History == | == History == | ||
The science of the tertiary structure of proteins has progressed from one of [[hypothesis]] to one of detailed definition. Although [[Hermann Emil Fischer|Emil Fischer]] had suggested proteins were made of [[polypeptide chain]]s and amino acid side chains, it was [[Dorothy Maud Wrinch]] who incorporated [[geometry]] into the prediction of [[protein structure]]s. Wrinch demonstrated this with the [[Cyclol|''Cyclol'' model]], the first prediction of the structure of a [[globular protein]].<ref>Senechal | The science of the tertiary structure of proteins has progressed from one of [[hypothesis]] to one of detailed definition. Although [[Hermann Emil Fischer|Emil Fischer]] had suggested proteins were made of [[polypeptide chain]]s and amino acid side chains, it was [[Dorothy Maud Wrinch]] who incorporated [[geometry]] into the prediction of [[protein structure]]s. Wrinch demonstrated this with the [[Cyclol|''Cyclol'' model]], the first prediction of the structure of a [[globular protein]].<ref>{{cite book |last1=Senechal |first1=Marjorie |title=I Died for Beauty: Dorothy Wrinch and the Cultures of Science |date=2012 |publisher=Oxford University Press |location=New York |isbn=0-19-991083-9 |chapter=The Cyclol Model |url=https://books.google.com/books?id=KE0k-reQCP8C&q=dorothy+wrinch}}</ref> Under favorable conditions, such as confident knowledge of [[secondary structure]], contemporary methods are sometimes able to predict the tertiary structure of small proteins (<120 residues) ''de novo'' to within 5 [[Angstrom|Å]] (0.5 nm).{{Citation needed|date=February 2007}}{{Update inline|date=October 2025|reason=Requires updating given the progress in [[protein structure prediction]] over the last 20 years}} | ||
== Determinants == | == Determinants == | ||
{{Main article|Protein folding}} | {{Main article|Protein folding}} | ||
=== Stability of native states === | === Stability of native states === | ||
{{See also|Equilibrium unfolding}} | {{See also|Equilibrium unfolding}} | ||
A protein folded into its [[native state]] or [[chemical conformation|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 [[cell (biology)|cellular]] environment. Because many similar conformations will have similar energies, protein structures are [[Protein dynamics|dynamic]], fluctuating between these similar structures. | A protein folded into its [[native state]] or [[chemical conformation|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 [[cell (biology)|cellular]] environment. Because many similar conformations will have similar energies, protein structures are [[Protein dynamics|dynamic]], fluctuating between these similar structures. | ||
| Line 20: | Line 19: | ||
[[Globular protein]]s have a core of [[hydrophobic]] amino acid residues and a surface region of [[water]]-exposed, charged, [[hydrophilic]] residues. This arrangement may stabilize interactions within the tertiary structure. For example, in [[secrete]]d proteins, which are not bathed in [[cytoplasm]], [[disulfide bond]]s between [[cysteine]] residues help to maintain the tertiary structure. There is a commonality of stable tertiary structures seen in proteins of diverse function and diverse [[molecular evolution|evolution]]. For example, the [[TIM barrel]], named for the enzyme [[triosephosphateisomerase]], is a common tertiary structure as is the highly stable, [[dimer (chemistry)|dimeric]], [[coiled coil]] structure. Hence, proteins may be classified by the structures they hold. Databases of proteins which use such a classification include ''[[Structural Classification of Proteins|SCOP]]'' and ''[[CATH]]''. | [[Globular protein]]s have a core of [[hydrophobic]] amino acid residues and a surface region of [[water]]-exposed, charged, [[hydrophilic]] residues. This arrangement may stabilize interactions within the tertiary structure. For example, in [[secrete]]d proteins, which are not bathed in [[cytoplasm]], [[disulfide bond]]s between [[cysteine]] residues help to maintain the tertiary structure. There is a commonality of stable tertiary structures seen in proteins of diverse function and diverse [[molecular evolution|evolution]]. For example, the [[TIM barrel]], named for the enzyme [[triosephosphateisomerase]], is a common tertiary structure as is the highly stable, [[dimer (chemistry)|dimeric]], [[coiled coil]] structure. Hence, proteins may be classified by the structures they hold. Databases of proteins which use such a classification include ''[[Structural Classification of Proteins|SCOP]]'' and ''[[CATH]]''. | ||
Folding [[Chemical kinetics|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 [[proteolysis|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]]. | Folding [[Chemical kinetics|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 [[proteolysis|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]]. | ||
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]].<ref name="whis">{{cite journal |last1=Whisstock |first1=James C |last2=Bottomley |first2=Stephen P |title=Molecular gymnastics: serpin structure, folding and misfolding |journal=Current Opinion in Structural Biology |date=December 2006 |volume=16 |issue=6 |pages=761–768 |doi=10.1016/j.sbi.2006.10.005 | pmid = 17079131}}</ref><ref>{{cite journal |last1=Gettins |first1=Peter G. W. |title=Serpin Structure, Mechanism, and Function |journal=Chemical Reviews |date=1 December 2002 |volume=102 |issue=12 |pages=4751–4804 |doi=10.1021/cr010170 |pmid=12475206}}</ref><ref>{{cite journal |last1=Whisstock |first1=James C |last2=Skinner |first2=Richard |last3=Carrell |first3=Robin W |last4=Lesk |first4=Arthur M |title=Conformational changes in serpins: I. the native and cleaved conformations of α 1 -antitrypsin 1 1Edited by J. M. Thornton |journal=Journal of Molecular Biology |date=February 2000 |volume=296 |issue=2 |pages=685–699 |doi=10.1006/jmbi.1999.3520 |pmid=10669617}}</ref> | |||
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]].<ref name="whis">{{cite journal | | |||
=== Chaperone proteins === | === Chaperone proteins === | ||
| Line 33: | Line 30: | ||
=== Ligand binding === | === Ligand binding === | ||
The structure of a protein, such as an [[enzyme]], may change upon binding of its natural ligands, for example a [[Cofactor (biochemistry)|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.<ref>{{cite journal| | The structure of a protein, such as an [[enzyme]], may change upon binding of its natural ligands, for example a [[Cofactor (biochemistry)|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.<ref>{{cite journal |last1=Seeliger |first1=Daniel |last2=de Groot |first2=Bert L. |title=Conformational Transitions upon Ligand Binding: Holo-Structure Prediction from Apo Conformations |journal=PLoS Computational Biology |date=8 January 2010 |volume=6 |issue=1 |article-number=e1000634 |doi=10.1371/journal.pcbi.1000634 |pmid=20066034|pmc=2796265|bibcode=2010PLSCB...6E0634S |doi-access=free }}</ref> | ||
Structure stabilized by the formation of weak bonds between amino acid side chains | Structure stabilized by the formation of weak bonds between amino acid side chains | ||
| Line 56: | Line 53: | ||
=== Dual polarisation interferometry === | === Dual polarisation interferometry === | ||
[[Dual polarisation interferometry]] provides complementary information about surface captured proteins. It assists in determining structure and conformation changes over time. | [[Dual polarisation interferometry]] provides complementary information about surface captured proteins. It assists in determining structure and conformation changes over time. | ||
=== Prediction algorithm === | === Prediction algorithm === | ||
The [[Folding@home]] project at the [[University of Pennsylvania]] is a [[distributed computing]] research effort which uses approximately 5 [[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.<ref>{{Cite web |title=Folding@home – Fighting disease with a world wide distributed super computer. |url=https://foldingathome.org/ |access-date=2024-04-23 |language=en-US}}</ref><ref>{{Cite web |title=Bowman Lab – University of Pennsylvania |url=https://bowmanlab.seas.upenn.edu/ |access-date=2024-04-23 |language=en-US}}</ref> | The [[Folding@home]] project at the [[University of Pennsylvania]] is a [[distributed computing]] research effort which uses approximately 5 [[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.<ref>{{Cite web |title=Folding@home – Fighting disease with a world wide distributed super computer. |url=https://foldingathome.org/ |access-date=2024-04-23 |language=en-US}}</ref><ref>{{Cite web |title=Bowman Lab – University of Pennsylvania |url=https://bowmanlab.seas.upenn.edu/ |access-date=2024-04-23 |language=en-US}}</ref> | ||
A list of software for protein tertiary structure prediction can be found at | A list of software for protein tertiary structure prediction can be found at [[List of protein structure prediction software]]. | ||
[[List of protein structure prediction software]]. | |||
== See also == | == See also == | ||
Latest revision as of 04:49, 5 October 2025
Template:Short description Script error: No such module "about".
Template:Refimprove Template:Protein structure
Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single 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 hypothesis to one of detailed definition. Although Emil Fischer had suggested proteins were made of polypeptide chains and amino acid side chains, it was Dorothy Maud Wrinch who incorporated geometry into the prediction of protein structures. Wrinch demonstrated this with the Cyclol model, the first prediction of the structure of a globular protein.[4] Under favorable conditions, such as confident knowledge of secondary structure, contemporary methods are sometimes able to predict the tertiary structure of small proteins (<120 residues) de novo to within 5 Å (0.5 nm).Script error: No such module "Unsubst".Template:Update inline
Determinants
Stability of native states
Script error: No such module "Labelled list hatnote". A protein folded into its native state or 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.
Globular proteins have a core of hydrophobic amino acid residues and a surface region of water-exposed, charged, hydrophilic residues. This arrangement may stabilize interactions within the tertiary structure. For example, in secreted proteins, which are not bathed in cytoplasm, disulfide bonds between cysteine residues help to maintain the tertiary structure. There is a commonality of stable tertiary structures seen in proteins of diverse function and diverse evolution. For example, the TIM barrel, named for the enzyme triosephosphateisomerase, 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 include SCOP and CATH.
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.
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 thermodynamically stable and that a protein will reach its native state, given its chemical kinetics, before it is translated. Protein chaperones 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, the prokaryotic GroEL/GroES system of proteins and the homologous eukaryotic heat shock proteins (the Hsp60/Hsp10 system).
Cytoplasmic environment
Prediction of protein tertiary structure relies on knowing the protein's primary structure and comparing the possible predicted tertiary structure with known tertiary structures in 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.
Prediction algorithm
The Folding@home project at the University of Pennsylvania is a distributed computing research effort which uses approximately 5 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]
A list of software for protein tertiary structure prediction can be found at List of protein structure prediction software.
See also
- Folding (chemistry)
- I-TASSER
- Nucleic acid tertiary structure
- Protein contact map
- Proteopedia
- Structural biology
- Structural motif
- Protein tandem repeats
References
External links
- Protein Data Bank
- Display, analyse and superimpose protein 3D structures
- Alphabet of protein structures.
- Display, analyse and superimpose protein 3D structures
- WWW-based course teaching elementary protein bioinformatics
- Critical Assessment of Structure Prediction (CASP)
- Structural Classification of Proteins (SCOP)
- CATH Protein Structure Classification
- DALI/FSSP software and database of superposed protein structures
- TOPOFIT-DB Invariant Structural Cores between proteins
- PDBWiki — PDBWiki Home Page – a website for community annotation of PDB structures.
Script error: No such module "Navbox". Template:Biomolecular structure
- ↑ Template:GoldBookRef
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".