Protein structure

1 Levels of protein structure

Protein structure

Protein structure is the biomolecular structure of a

protein molecule. Proteins are polymers specically
polypeptides -sequences formed from various L--amino
acids. Each unit of a protein is called an amino acid
residue because it is the residue of every amino acid that
forms the protein by losing a water molecule. By convention, a chain under 40 residues is often identied as a
peptide, rather than a protein. To be able to perform their
biological function, proteins fold into one or more specic spatial conformations, driven by a number of noncovalent interactions such as hydrogen bonding, ionic interactions, Van der Waals forces, and hydrophobic packing. To understand the functions of proteins at a molecular level, it is often necessary to determine their threedimensional structure. This is the topic of the scientic
eld of structural biology, which employs techniques such Protein structure, from primary to quaternary structure.
as X-ray crystallography, NMR spectroscopy, and dual
polarisation interferometry to determine the structure of There are four distinct levels of protein structure.
proteins.

1.1 Amino acid residues

Protein structures range in size from tens to several thousand residues.[1] By physical size, proteins are classied
as nanoparticles, between 1100 nm. Very large aggregates can be formed from protein subunits. For example, many thousands of actin molecules assemble into a
microlament.

Main article: Amino acid

Main article: Proteinogenic amino acid
Each -amino acid consists of a backbone part that is
present in all the amino acid types, and a side chain that
is unique to each type of residue. An exception from
this rule is proline. Because the carbon atom is bound to
four dierent groups it is chiral, however only one of the
isomers occur in biological proteins. Glycine however, is

A protein may undergo reversible structural changes in

performing its biological function. The alternative structures of the same protein are referred to as dierent
conformations, and transitions between them are called
conformational changes.
1

LEVELS OF PROTEIN STRUCTURE

not chiral since its side chain is a hydrogen atom. A simple mnemonic for correct L-form is CORN": when the
C atom is viewed with the H in front, the residues read
CO-R-N in a clockwise direction.

1.2

Primary structure

Main article: Protein primary structure

The primary structure of a protein refers to the linear sequence of amino acids in the polypeptide chain. The primary structure is held together by covalent bonds such
as peptide bonds, which are made during the process of
protein biosynthesis or translation. The two ends of the
polypeptide chain are referred to as the carboxyl terminus (C-terminus) and the amino terminus (N-terminus)
based on the nature of the free group on each extremity.
Counting of residues always starts at the N-terminal end
(NH2 -group), which is the end where the amino group
is not involved in a peptide bond. The primary structure
of a protein is determined by the gene corresponding to
the protein. A specic sequence of nucleotides in DNA is
transcribed into mRNA, which is read by the ribosome in
a process called translation. The sequence of amino acids
was discovered by Frederick Sanger. The sequence of a
protein is unique to that protein, and denes the structure
and function of the protein. The sequence of a protein can
be determined by methods such as Edman degradation or
tandem mass spectrometry. Often, however, it is read directly from the sequence of the gene using the genetic
code. We know that there are over 10,000 proteins in the
human body which are composed of dierent arrangements of 20 types of amino acid residues. It is strictly
recommended to use the words amino acid residues
when discussing proteins because when a peptide bond
is formed, a water molecule is lost, so proteins are made
up of amino acid residues. Post-translational modication such as disulde bond formation, phosphorylations
and glycosylations are usually also considered a part of
the primary structure, and cannot be read from the gene.
For example, insulin is composed of 51 amino acids in 2 An alpha-helix with hydrogen bonds (yellow dots)
chains. One chain has 31 amino acids, and the other has
20 amino acids.
Both the alpha helix and the beta sheet represent a way
of saturating all the hydrogen bond donors and acceptors
1.3 Secondary structure
in the peptide backbone. Some parts of the protein are
ordered but do not form any regular structures. They
Main article: Protein secondary structure
should not be confused with random coil, an unfolded
polypeptide chain lacking any xed three-dimensional
Secondary structure refers to highly regular local sub- structure. Several sequential secondary structures may
[3]
structures. Two main types of secondary structure, the form a "supersecondary unit".
alpha helix and the beta strand or beta sheets, were suggested in 1951 by Linus Pauling and coworkers.[2] These
secondary structures are dened by patterns of hydrogen 1.4 Tertiary structure
bonds between the main-chain peptide groups. They have
a regular geometry, being constrained to specic values Main article: Protein tertiary structure
of the dihedral angles and on the Ramachandran plot.

2.1

Structural domain

Tertiary structure refers to the three-dimensional structure of a single, double, or triple bonded protein molecule.
The alpha-helixes and beta pleated-sheets are folded into
a compact globular structure. The folding is driven by
the non-specic hydrophobic interactions, the burial of
hydrophobic residues from water, but the structure is stable only when the parts of a protein domain are locked
into place by specic tertiary interactions, such as salt
bridges, hydrogen bonds, and the tight packing of side
chains and disulde bonds. The disulde bonds are extremely rare in cytosolic proteins, since the cytosol (intracellular uid) is generally a reducing environment.

1.5

Quaternary structure

Main article: Protein quaternary structure

Quaternary structure is the three-dimensional structure
of a multi-subunit protein and how the subunits t together. In this context, the quaternary structure is stabilized by the same non-covalent interactions and disulde bonds as the tertiary structure. Complexes of two
or more polypeptides (i.e. multiple subunits) are called
multimers. Specically it would be called a dimer if
it contains two subunits, a trimer if it contains three
subunits, a tetramer if it contains four subunits, and a
pentamer if it contains ve subunits. The subunits are frequently related to one another by symmetry operations,
such as a 2-fold axis in a dimer. Multimers made up of
identical subunits are referred to with a prex of homo" (e.g. a homotetramer) and those made up of dierent
subunits are referred to with a prex of hetero-", for example, a heterotetramer, such as the two alpha and two
beta chains of hemoglobin.

3
are many fewer dierent domains, structural motifs and
folds.

2.1 Structural domain

A structural domain is an element of the proteins overall
structure that is self-stabilizing and often folds independently of the rest of the protein chain. Many domains
are not unique to the protein products of one gene or one
gene family but instead appear in a variety of proteins.
Domains often are named and singled out because they
gure prominently in the biological function of the protein they belong to; for example, the "calcium-binding
domain of calmodulin". Because they are independently
stable, domains can be swapped by genetic engineering
between one protein and another to make chimera proteins.

2.2 Structural and sequence motif

The structural and sequence motifs refer to short segments of protein three-dimensional structure or amino
acid sequence that were found in a large number of different proteins.

2.3 Supersecondary structure

The supersecondary structure refers to a specic combination of secondary structure elements, such as betaalpha-beta units or a helix-turn-helix motif. Some of
them may be also referred to as structural motifs.

Domains, motifs, and folds in

2.4 Protein fold
protein structure
A protein fold refers to the general protein architecture,
like a helix bundle, beta-barrel, Rossman fold or dierent
folds provided in the Structural Classication of Proteins database.[4]

2.5 Superdomain

Protein domains. The two shown protein structures share a common domain (maroon), the PH domain, which is involved in
phosphatidylinositol (3,4,5)-trisphosphate binding

Proteins are frequently described as consisting of several structural units. These units include domains, motifs,
and folds. Despite the fact that there are about 100,000
dierent proteins expressed in eukaryotic systems, there

A superdomain consists of two or more nominally unrelated structural domains that are inherited as a single unit
and occur in dierent proteins.[5] An example is provided
by the protein tyrosine phosphatase domain and C2 domain pair in PTEN, several tensin proteins, auxilin and
proteins in plants and fungi. The PTP-C2 superdomain
evidently came into existence prior to the divergence of
fungi, plants and animals is therefore likely to be about
1.5 billion years old.

REFERENCES

Protein folding

complexes such as virus coat proteins and amyloid bers.

A more qualitative picture of protein structure is often
obtained by proteolysis, which is also useful to screen for
Main article: Protein folding
more crystallizable protein samples. Novel implementations of this approach, including fast parallel proteolysis
Once translated by a ribosome, each polypeptide folds (FASTpp), can probe the structured fraction and its stainto its characteristic three-dimensional structure from a bility without the need for purication.[9]
random coil.[6] Since the fold is maintained by a network
of interactions between amino acids in the polypeptide,
the native state of the protein chain is determined by the
5 Structure classication
amino acid sequence (Annsens dogma).[7]

Protein structure determination

Protein structures can be grouped based on their similarity or a common evolutionary origin. The Structural Classication of Proteins database[10] and CATH database[11]
provide two dierent structural classications of proteins. Shared structure between proteins is considered evidence of evolutionary relatedness between proteins and
is used group proteins together into protein superfamilies.[12]

6 Computational prediction of protein structure

Main article: Protein structure prediction

Examples of protein structures from the PDB

Around 90% of the protein structures available in the

Protein Data Bank have been determined by X-ray crystallography. This method allows one to measure the
three-dimensional (3-D) density distribution of electrons
in the protein, in the crystallized state, and thereby infer
the 3-D coordinates of all the atoms to be determined to
a certain resolution. Roughly 9% of the known protein
structures have been obtained by nuclear magnetic resonance techniques. The secondary structure composition
can be determined via circular dichroism. Vibrational
spectroscopy can also be used to characterize the conformation of peptides, polypeptides, and proteins.[8] Cryoelectron microscopy has recently become a means of determining protein structures to high resolution, less than
5 angstroms or 0.5 nanometer, and is anticipated to increase in power as a tool for high resolution work in
the next decade. This technique is still a valuable resource for researchers working with very large protein

The generation of a protein sequence is much easier than

the determination of a protein structure. However, the
structure of a protein gives much more insight in the function of the protein than its sequence. Therefore, a number of methods for the computational prediction of protein structure from its sequence have been developed.[13]
Ab initio prediction methods use just the sequence of
the protein. Threading and homology modeling methods can build a 3-D model for a protein of unknown
structure from experimental structures of evolutionarilyrelated proteins, called a protein family.

7 References
[1] Brocchieri L, Karlin S (2005-06-10). Protein length in
eukaryotic and prokaryotic proteomes. Nucleic Acids
Research 33 (10): 33903400. doi:10.1093/nar/gki615.
PMC 1150220. PMID 15951512.
[2] Pauling L, Corey RB, Branson HR (1951). The structure
of proteins; two hydrogen-bonded helical congurations
of the polypeptide chain. Proc Natl Acad Sci USA 37 (4):
205211. doi:10.1073/pnas.37.4.205. PMC 1063337.
PMID 14816373.
[3] Chiang YS, Gelfand TI, Kister AE, Gelfand IM
(2007). New classication of supersecondary structures of sandwich-like proteins uncovers strict patterns
of strand assemblage.. Proteins. 68 (4): 915921.
doi:10.1002/prot.21473. PMID 17557333.

[4] Govindarajan S, Recabarren R, Goldstein RA.

(17 September 1999).
Estimating the total number of protein folds..
Proteins.
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(4):
408414.
doi:10.1002/(SICI)10970134(19990601)35:4<408::AID-PROT4>3.0.CO;2-A.
PMID 10382668.
[5] Haynie DT, Xue B (2015). Superdomain in the protein
structure hierarchy: the case of PTP-C2.. Protein Science. doi:10.1002/pro.2664. PMID 25694109.
[6] Alberts, Bruce; Alexander Johnson; Julian Lewis; Martin
Ra; Keith Roberts; Peter Walters (2002). The Shape
and Structure of Proteins. Molecular Biology of the Cell;
Fourth Edition. New York and London: Garland Science.
ISBN 0-8153-3218-1.
[7] Annsen, C. (1972). The formation and stabilization of
protein structure. Biochem. J. 128 (4): 73749. PMC
1173893. PMID 4565129.
[8] Krimm, Samuel; Bandekar, J. (1986). Vibrational Spectroscopy and Conformation of Peptides, Polypeptides, and
Proteins. Advances in Protein Chemistry. Advances in
Protein Chemistry 38 (C): 181364. doi:10.1016/S00653233(08)60528-8. ISBN 9780120342389.
[9] Minde DP, Maurice MM, Rdiger SG (2012).
Uversky, Vladimir N, ed.
Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp. PLoS ONE 7 (10): e46147.
doi:10.1371/journal.pone.0046147.
PMC 3463568.
PMID 23056252.
[10] Murzin, A. G.; Brenner, S.; Hubbard, T.; Chothia, C.
(1995). SCOP: A structural classication of proteins
database for the investigation of sequences and structures. Journal of Molecular Biology 247 (4): 536540.
doi:10.1016/S0022-2836(05)80134-2. PMID 7723011.
[11] Orengo, C. A.; Michie, A. D.; Jones, S.; Jones, D. T.;
Swindells, M. B.; Thornton, J. M. (1997). CATH-a hierarchic classication of protein domain structures.
Structure (London, England : 1993) 5 (8): 10931108.
doi:10.1016/S0969-2126(97)00260-8. PMID 9309224.
[12] Holm, L; Rosenstrm, P (July 2010). Dali server: conservation mapping in 3D.. Nucleic Acids Research 38
(Web Server issue): W5459. doi:10.1093/nar/gkq366.
PMID 20457744.
[13] Zhang Y (2008). Progress and challenges in protein
structure prediction. Curr Opin Struct Biol 18 (3): 342
348. doi:10.1016/j.sbi.2008.02.004. PMC 2680823.
PMID 18436442.

Further reading
50 Years of Protein Structure Determination Timeline - HTML Version - National Institute of General
Medical Sciences at NIH

9 TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES

Text and image sources, contributors, and licenses

9.1

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Protein structure Source: http://en.wikipedia.org/wiki/Protein%20structure?oldid=649694311 Contributors: AxelBoldt, Ghakko, Lexor,

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9.2

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File:Alpha_helix.png Source: http://upload.wikimedia.org/wikipedia/commons/7/75/Alpha_helix.png License: CC-BY-SA-3.0 Contributors: en:Alpha.png Original artist: Zsolt Bikadi / en:User:Bikadi
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levels_en.svg License: Public domain Contributors: Own work based on what i could get. in between others:[1], [2], [3], [4], [5], [6],[7],
[8]. Original artist: LadyofHats
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