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This article is about a class of molecules. For protein genetic code. In general, the genetic code species 20
as a nutrient, see Protein (nutrient). For other uses, see standard amino acids; however, in certain organisms the
Protein (disambiguation).
genetic code can include selenocysteine andin certain
archaeapyrrolysine. Shortly after or even during synthesis, the residues in a protein are often chemically modied by posttranslational modication, which alters the
physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Sometimes proteins have non-peptide groups attached, which
can be called prosthetic groups or cofactors. Proteins can
also work together to achieve a particular function, and
they often associate to form stable protein complexes.
Once formed, proteins only exist for a certain period of
time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and
covers a wide range. They can exist for minutes or years
with an average lifespan of 12 days in mammalian cells.
Abnormal and or misfolded proteins are degraded more
rapidly either due to being targeted for destruction or due
to being unstable.
Like other biological macromolecules such as
polysaccharides and nucleic acids, proteins are essential parts of organisms and participate in virtually
every process within cells. Many proteins are enzymes
that catalyze biochemical reactions and are vital to
metabolism. Proteins also have structural or mechanical
functions, such as actin and myosin in muscle and the
proteins in the cytoskeleton, which form a system of
scaolding that maintains cell shape. Other proteins
are important in cell signaling, immune responses, cell
adhesion, and the cell cycle. Proteins are also necessary
in animals diets, since animals cannot synthesize all the
amino acids they need and must obtain essential amino
acids from food. Through the process of digestion,
animals break down ingested protein into free amino
acids that are then used in metabolism.
SYNTHESIS
Biochemistry
terminus or amino terminus. The words protein, polypeptide, and peptide are a little ambiguous and can overMain articles: Biochemistry, Amino acid and peptide lap in meaning. Protein is generally used to refer to the
complete biological molecule in a stable conformation,
bond
Most proteins consist of linear polymers built from series whereas peptide is generally reserved for a short amino
acid oligomers often lacking a stable three-dimensional
structure. However, the boundary between the two is
not well dened and usually lies near 2030 residues.[5]
Polypeptide can refer to any single linear chain of amino
acids, usually regardless of length, but often implies an
absence of a dened conformation.
2 Synthesis
2.1 Biosynthesis
Main article: Protein biosynthesis
Proteins are assembled from amino acids using informaChemical structure of the peptide bond (bottom) and the threedimensional structure of a peptide bond between an alanine and
an adjacent amino acid (top/inset)
GTGCATCTGACTCCTGAGGAGAAG
CACGTAGACTGAGGACTCCTCTTC
DNA
(transcription)
GUGCAUCUGACUCCUGAGGAGAAG
RNA
(translation)
protein
3
Genes encoded in DNA are rst transcribed into pre- 3 Structure
messenger RNA (mRNA) by proteins such as RNA polymerase. Most organisms then process the pre-mRNA Main article: Protein structure
(also known as a primary transcript) using various forms Further information: Protein structure prediction
of Post-transcriptional modication to form the mature Most proteins fold into unique 3-dimensional structures.
mRNA, which is then used as a template for protein synthesis by the ribosome. In prokaryotes the mRNA may
either be used as soon as it is produced, or be bound by
a ribosome after having moved away from the nucleoid.
In contrast, eukaryotes make mRNA in the cell nucleus
and then translocate it across the nuclear membrane into
the cytoplasm, where protein synthesis then takes place.
The rate of protein synthesis is higher in prokaryotes
than eukaryotes and can reach up to 20 amino acids per
second.[7]
The crystal structure of the chaperonin. Chaperonins assist pro-
2.2
Chemical synthesis
4 CELLULAR FUNCTIONS
disulde bonds, and even posttranslational modications. The term tertiary structure is often used as
synonymous with the term fold. The tertiary structure is what controls the basic function of the protein.
Quaternary structure: the structure formed by several protein molecules (polypeptide chains), usually
called protein subunits in this context, which function as a single protein complex.
both of which can produce information at atomic resolution. However, NMR experiments are able to provide information from which a subset of distances between pairs
of atoms can be estimated, and the nal possible conformations for a protein are determined by solving a distance
geometry problem. Dual polarisation interferometry is a
quantitative analytical method for measuring the overall
protein conformation and conformational changes due to
interactions or other stimulus. Circular dichroism is another laboratory technique for determining internal beta
sheet/ helical composition of proteins. Cryoelectron microscopy is used to produce lower-resolution structural
information about very large protein complexes, including assembled viruses;[18] a variant known as electron
crystallography can also produce high-resolution information in some cases, especially for two-dimensional
crystals of membrane proteins.[19] Solved structures are
usually deposited in the Protein Data Bank (PDB), a
freely available resource from which structural data about
thousands of proteins can be obtained in the form of
Cartesian coordinates for each atom in the protein.[20]
3.1
Structure determination
Discovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important
clues about how the protein performs its function. Common experimental methods of structure determination
include X-ray crystallography and NMR spectroscopy,
4.2
nes the binding site pocket, and by the chemical properties of the surrounding amino acids side chains. Protein binding can be extraordinarily tight and specic; for
example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<1015 M) but does not bind at all to its amphibian
homolog onconase (>1 M). Extremely minor chemical
changes such as the addition of a single methyl group to a
binding partner can sometimes suce to nearly eliminate
binding; for example, the aminoacyl tRNA synthetase
specic to the amino acid valine discriminates against the
very similar side chain of the amino acid isoleucine.[24]
5
highly specic and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism, as well as manipulating
DNA in processes such as DNA replication, DNA repair, and transcription. Some enzymes act on other proteins to add or remove chemical groups in a process
known as posttranslational modication. About 4,000 reactions are known to be catalyzed by enzymes.[28] The
rate acceleration conferred by enzymatic catalysis is often
enormousas much as 1017 -fold increase in rate over the
uncatalyzed reaction in the case of orotate decarboxylase
(78 million years without the enzyme, 18 milliseconds
with the enzyme).[29]
The molecules bound and acted upon by enzymes are
called substrates. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction
of the residues that come in contact with the substrate,
and an even smaller fractionthree to four residues on
averagethat are directly involved in catalysis.[30] The
region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.
Dirigent proteins are members of a class of proteins
which dictate the stereochemistry of a compound synthesized by other enzymes.
Proteins can bind to other proteins as well as to smallmolecule substrates. When proteins bind specically to
other copies of the same molecule, they can oligomerize
to form brils; this process occurs often in structural proteins that consist of globular monomers that self-associate
to form rigid bers. Proteinprotein interactions also regulate enzymatic activity, control progression through the
cell cycle, and allow the assembly of large protein complexes that carry out many closely related reactions with
a common biological function. Proteins can also bind to,
or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes
in proteins allows the construction of enormously complex signaling networks.[25] Importantly, as interactions
between proteins are reversible, and depend heavily on
the availability of dierent groups of partner proteins to
form aggregates that are capable to carry out discrete sets
of function, study of the interactions between specic
proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish
particular cell types.[26][27]
4.1
Enzymes
The best-known role of proteins in the cell is as enzymes, Many proteins are involved in the process of cell sigwhich catalyze chemical reactions. Enzymes are usually naling and signal transduction. Some proteins, such as
5 METHODS OF STUDY
Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone
has a hydrophobic core through which polar or charged
molecules cannot diuse. Membrane proteins contain internal channels that allow such molecules to enter and exit
the cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and
sodium channels often discriminate for only one of the
two ions.[35]
4.3
Structural proteins
5.3
Proteomics
5.2
Cellular localization
7
vacuoles, mitochondria, chloroplasts, plasma membrane,
etc. With the use of uorescently tagged versions of these
markers or of antibodies to known markers, it becomes
much simpler to identify the localization of a protein of
interest. For example, indirect immunouorescence will
allow for uorescence colocalization and demonstration
of location. Fluorescent dyes are used to label cellular
compartments for a similar purpose.[43]
Other possibilities exist, as well.
For example,
immunohistochemistry usually utilizes an antibody to one
or more proteins of interest that are conjugated to enzymes yielding either luminescent or chromogenic signals
that can be compared between samples, allowing for localization information. Another applicable technique is
cofractionation in sucrose (or other material) gradients
using isopycnic centrifugation.[44] While this technique
does not prove colocalization of a compartment of known
density and the protein of interest, it does increase the
likelihood, and is more amenable to large-scale studies.
Finally, the gold-standard method of cellular localization
is immunoelectron microscopy. This technique also uses
an antibody to the protein of interest, along with classical
electron microscopy techniques. The sample is prepared
for normal electron microscopic examination, and then
treated with an antibody to the protein of interest that is
conjugated to an extremely electro-dense material, usually gold. This allows for the localization of both ultrastructural details as well as the protein of interest.[45]
Through another genetic engineering application known
as site-directed mutagenesis, researchers can alter the
protein sequence and hence its structure, cellular localization, and susceptibility to regulation. This technique even
allows the incorporation of unnatural amino acids into
proteins, using modied tRNAs,[46] and may allow the
rational design of new proteins with novel properties.[47]
5.3 Proteomics
Proteins in dierent cellular compartments and structures tagged
with green uorescent protein (here, white)
6 NUTRITION
5.4
Bioinformatics
to provide plausible models for proteins whose structures have not yet been determined experimentally.[54]
The most successful type of structure prediction, known
as homology modeling, relies on the existence of a template structure with sequence similarity to the protein
being modeled; structural genomics goal is to provide
sucient representation in solved structures to model
most of those that remain.[55] Although producing accurate models remains a challenge when only distantly related template structures are available, it has been suggested that sequence alignment is the bottleneck in this
process, as quite accurate models can be produced if a
perfect sequence alignment is known.[56] Many structure prediction methods have served to inform the emerging eld of protein engineering, in which novel protein folds have already been designed.[57] A more complex computational problem is the prediction of intermolecular interactions, such as in molecular docking and
proteinprotein interaction prediction.[58]
The processes of protein folding and binding can be simulated using such technique as molecular mechanics, in
particular, molecular dynamics and Monte Carlo, which
increasingly take advantage of parallel and distributed
computing (Folding@home project;[59] molecular modeling on GPU). The folding of small alpha-helical protein domains such as the villin headpiece[60] and the
HIV accessory protein[61] have been successfully simulated in silico, and hybrid methods that combine standard molecular dynamics with quantum mechanics calculations have allowed exploration of the electronic states
of rhodopsins.[62]
6 Nutrition
Further information: Protein (nutrient)
In animals, amino acids are obtained through the consumption of foods containing protein. Ingested proMain articles: Protein structure prediction and List of teins are then broken down into amino acids through
protein structure prediction software
digestion, which typically involves denaturation of the
protein through exposure to acid and hydrolysis by enComplementary to the eld of structural genomics, pro- zymes called proteases. Some ingested amino acids are
tein structure prediction seeks to develop ecient ways used for protein biosynthesis, while others are converted
9
to glucose through gluconeogenesis, or fed into the citric
acid cycle. This use of protein as a fuel is particularly important under starvation conditions as it allows the bodys
own proteins to be used to support life, particularly those
found in muscle.[63] Amino acids are also an important
dietary source of nitrogen.
10
Protein design
Proteopathy
Proteopedia
Proteolysis
Protein superfamily
Protein structure
Protein fold
REFERENCES
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10
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10 Textbooks
Branden C, Tooze J (1999). Introduction to Protein
Structure. New York: Garland Pub. ISBN 0-81532305-0.
11.2
11
External links
11.1
11.2
An Introduction to Proteins from HOPES (Huntingtons Disease Outreach Project for Education at
Stanford)
Proteins: Biogenesis to Degradation The Virtual
Library of Biochemistry and Cell Biology
13
14
12
12
12.1
Protein Source: http://en.wikipedia.org/wiki/Protein?oldid=646143808 Contributors: AxelBoldt, Magnus Manske, Marj Tiefert, Mav,
Bryan Derksen, Tarquin, Taw, Malcolm Farmer, Andre Engels, Toby Bartels, PierreAbbat, Karen Johnson, Ben-Zin, Robert Foley, AdamRetchless, Netesq, Mbecker, DennisDaniels, Spi, Dwmyers, Lir, Michael Hardy, Erik Zachte, Lexor, Ixfd64, Fruge, Cyde, 168...,
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