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6250 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 diffuse . 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 .
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34.514644622802734 87 WikiText2
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6251 = = = Structural proteins = = =
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6252 Structural proteins confer stiffness and rigidity to otherwise @-@ fluid biological components . Most structural proteins are fibrous proteins ; for example , collagen and elastin are critical components of connective tissue such as cartilage , and keratin is found in hard or filamentous structures such as hair , nails , feathers , hooves , and some animal shells . Some globular proteins can also play structural functions , for example , actin and tubulin are globular and soluble as monomers , but polymerize to form long , stiff fibers that make up the cytoskeleton , which allows the cell to maintain its shape and size .
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44.519317626953125 109 WikiText2
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6253 Other proteins that serve structural functions are motor proteins such as myosin , kinesin , and dynein , which are capable of generating mechanical forces . These proteins are crucial for cellular motility of single celled organisms and the sperm of many multicellular organisms which reproduce sexually . They also generate the forces exerted by contracting muscles and play essential roles in intracellular transport .
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39.66801071166992 65 WikiText2
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6254 = = Methods of study = =
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6255 The activities and structures of proteins may be examined in vitro , in vivo , and in silico . In vitro studies of purified proteins in controlled environments are useful for learning how a protein carries out its function : for example , enzyme kinetics studies explore the chemical mechanism of an enzyme 's catalytic activity and its relative affinity for various possible substrate molecules . By contrast , in vivo experiments can provide information about the physiological role of a protein in the context of a cell or even a whole organism . In silico studies use computational methods to study proteins .
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6256 = = = Protein purification = = =
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6257 To perform in vitro analysis , a protein must be purified away from other cellular components . This process usually begins with cell lysis , in which a cell 's membrane is disrupted and its internal contents released into a solution known as a crude lysate . The resulting mixture can be purified using ultracentrifugation , which fractionates the various cellular components into fractions containing soluble proteins ; membrane lipids and proteins ; cellular organelles , and nucleic acids . Precipitation by a method known as salting out can concentrate the proteins from this lysate . Various types of chromatography are then used to isolate the protein or proteins of interest based on properties such as molecular weight , net charge and binding affinity . The level of purification can be monitored using various types of gel electrophoresis if the desired protein 's molecular weight and isoelectric point are known , by spectroscopy if the protein has distinguishable spectroscopic features , or by enzyme assays if the protein has enzymatic activity . Additionally , proteins can be isolated according their charge using electrofocusing .
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30.08301544189453 184 WikiText2
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6258 For natural proteins , a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications . To simplify this process , genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity . Here , a " tag " consisting of a specific amino acid sequence , often a series of histidine residues ( a " His @-@ tag " ) , is attached to one terminus of the protein . As a result , when the lysate is passed over a chromatography column containing nickel , the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded . A number of different tags have been developed to help researchers purify specific proteins from complex mixtures .
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39.11405944824219 145 WikiText2
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6259 = = = Cellular localization = = =
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223.56044006347656 8 WikiText2
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6260 The study of proteins in vivo is often concerned with the synthesis and localization of the protein within the cell . Although many intracellular proteins are synthesized in the cytoplasm and membrane @-@ bound or secreted proteins in the endoplasmic reticulum , the specifics of how proteins are targeted to specific organelles or cellular structures is often unclear . A useful technique for assessing cellular localization uses genetic engineering to express in a cell a fusion protein or chimera consisting of the natural protein of interest linked to a " reporter " such as green fluorescent protein ( GFP ) . The fused protein 's position within the cell can be cleanly and efficiently visualized using microscopy , as shown in the figure opposite .
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34.432518005371094 127 WikiText2
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6261 Other methods for elucidating the cellular location of proteins requires the use of known compartmental markers for regions such as the ER , the Golgi , lysosomes or vacuoles , mitochondria , chloroplasts , plasma membrane , etc . With the use of fluorescently 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 immunofluorescence will allow for fluorescence colocalization and demonstration of location . Fluorescent dyes are used to label cellular compartments for a similar purpose .
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35.908817291259766 98 WikiText2
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6262 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 . 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 .
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74.74459838867188 99 WikiText2
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6263 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 .
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41.203758239746094 89 WikiText2
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6264 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 modified tRNAs , and may allow the rational design of new proteins with novel properties .
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73.46739196777344 63 WikiText2
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6265 = = = Proteomics = = =
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142.23333740234375 7 WikiText2
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6266 The total complement of proteins present at a time in a cell or cell type is known as its proteome , and the study of such large @-@ scale data sets defines the field of proteomics , named by analogy to the related field of genomics . Key experimental techniques in proteomics include 2D electrophoresis , which allows the separation of a large number of proteins , mass spectrometry , which allows rapid high @-@ throughput identification of proteins and sequencing of peptides ( most often after in @-@ gel digestion ) , protein microarrays , which allow the detection of the relative levels of a large number of proteins present in a cell , and two @-@ hybrid screening , which allows the systematic exploration of protein – protein interactions . The total complement of biologically possible such interactions is known as the interactome . A systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics .
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40.74896240234375 173 WikiText2
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6267 = = = Bioinformatics = = =
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6268 A vast array of computational methods have been developed to analyze the structure , function , and evolution of proteins .
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45.53030776977539 21 WikiText2
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6269 The development of such tools has been driven by the large amount of genomic and proteomic data available for a variety of organisms , including the human genome . It is simply impossible to study all proteins experimentally , hence only a few are subjected to laboratory experiments while computational tools are used to extrapolate to similar proteins . Such homologous proteins can be efficiently identified in distantly related organisms by sequence alignment . Genome and gene sequences can be searched by a variety of tools for certain properties . Sequence profiling tools can find restriction enzyme sites , open reading frames in nucleotide sequences , and predict secondary structures . Phylogenetic trees can be constructed and evolutionary hypotheses developed using special software like ClustalW regarding the ancestry of modern organisms and the genes they express . The field of bioinformatics is now indispensable for the analysis of genes and proteins .
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6270 = = = = Structure prediction and simulation = = = =
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138.373291015625 12 WikiText2
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6271 Complementary to the field of structural genomics , protein structure prediction seeks to develop efficient ways to provide plausible models for proteins whose structures have not yet been determined experimentally . 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 sufficient representation in solved structures to model most of those that remain . 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 . Many structure prediction methods have served to inform the emerging field of protein engineering , in which novel protein folds have already been designed . A more complex computational problem is the prediction of intermolecular interactions , such as in molecular docking and protein – protein interaction prediction .
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46.11254119873047 179 WikiText2
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6272 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 ; molecular modeling on GPU ) . The folding of small α @-@ helical protein domains such as the villin headpiece and the HIV accessory protein 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 .
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6273 = = = = Protein disorder and unstructure prediction = = = =
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357.5745849609375 13 WikiText2
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6274 Many proteins ( in Eucaryota ~ 33 % ) contain large unstructured but biologically functional segments and can be classified as intrinsically disordered proteins . Predicting and analysing protein disorder is , therefore , an important part of protein structure characterisation .
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105.47782135009766 42 WikiText2
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6275 = = Nutrition = =
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879.9429931640625 5 WikiText2
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6276 Most microorganisms and plants can biosynthesize all 20 standard amino acids , while animals ( including humans ) must obtain some of the amino acids from the diet . The amino acids that an organism cannot synthesize on its own are referred to as essential amino acids . Key enzymes that synthesize certain amino acids are not present in animals — such as aspartokinase , which catalyses the first step in the synthesis of lysine , methionine , and threonine from aspartate . If amino acids are present in the environment , microorganisms can conserve energy by taking up the amino acids from their surroundings and downregulating their biosynthetic pathways .
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20.306682586669922 112 WikiText2
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6277 In animals , amino acids are obtained through the consumption of foods containing protein . Ingested proteins are then broken down into amino acids through digestion , which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases . Some ingested amino acids are used for protein biosynthesis , while others are converted 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 body 's own proteins to be used to support life , particularly those found in muscle . Amino acids are also an important dietary source of nitrogen .
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19.973743438720703 117 WikiText2
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6278 = = History and etymology = =
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481.97613525390625 7 WikiText2
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6279 Proteins were recognized as a distinct class of biological molecules in the eighteenth century by Antoine Fourcroy and others , distinguished by the molecules ' ability to coagulate or flocculate under treatments with heat or acid . Noted examples at the time included albumin from egg whites , blood serum albumin , fibrin , and wheat gluten .
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68.4663314819336 58 WikiText2
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6280 Proteins were first described by the Dutch chemist Gerardus Johannes Mulder and named by the Swedish chemist Jöns Jacob Berzelius in 1838 . Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula , C400H620N100O120P1S1 . He came to the erroneous conclusion that they might be composed of a single type of ( very large ) molecule . The term " protein " to describe these molecules was proposed by Mulder 's associate Berzelius ; protein is derived from the Greek word πρώτειος ( proteios ) , meaning " primary " , " in the lead " , or " standing in front " , + -in . Mulder went on to identify the products of protein degradation such as the amino acid leucine for which he found a ( nearly correct ) molecular weight of 131 Da .
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46.497947692871094 148 WikiText2
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6281 Early nutritional scientists such as the German Carl von Voit believed that protein was the most important nutrient for maintaining the structure of the body , because it was generally believed that " flesh makes flesh . " Karl Heinrich Ritthausen extended known protein forms with the identification of glutamic acid . At the Connecticut Agricultural Experiment Station a detailed review of the vegetable proteins was compiled by Thomas Burr Osborne . Working with Lafayette Mendel and applying Liebig 's law of the minimum in feeding laboratory rats , the nutritionally essential amino acids were established . The work was continued and communicated by William Cumming Rose . The understanding of proteins as polypeptides came through the work of Franz Hofmeister and Hermann Emil Fischer . The central role of proteins as enzymes in living organisms was not fully appreciated until 1926 , when James B. Sumner showed that the enzyme urease was in fact a protein .
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59.99319076538086 158 WikiText2
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6282 The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study . Hence , early studies focused on proteins that could be purified in large quantities , e.g. , those of blood , egg white , various toxins , and digestive / metabolic enzymes obtained from slaughterhouses . In the 1950s , the Armour Hot Dog Co. purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists ; this gesture helped ribonuclease A become a major target for biochemical study for the following decades .
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47.967166900634766 99 WikiText2
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6283 Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding , an idea first put forth by William Astbury in 1933 . Later work by Walter Kauzmann on denaturation , based partly on previous studies by Kaj Linderstrøm @-@ Lang , contributed an understanding of protein folding and structure mediated by hydrophobic interactions .
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134.66331481933594 63 WikiText2
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6284 The first protein to be sequenced was insulin , by Frederick Sanger , in 1949 . Sanger correctly determined the amino acid sequence of insulin , thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains , colloids , or cyclols . He won the Nobel Prize for this achievement in 1958 .
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46.7577018737793 59 WikiText2
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6285 The first protein structures to be solved were hemoglobin and myoglobin , by Max Perutz and Sir John Cowdery Kendrew , respectively , in 1958 . As of 2016 , the Protein Data Bank has over 115 @,@ 000 atomic @-@ resolution structures of proteins . In more recent times , cryo @-@ electron microscopy of large macromolecular assemblies and computational protein structure prediction of small protein domains are two methods approaching atomic resolution .
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127.80892181396484 81 WikiText2
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6286 = = Textbooks = =
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816.0093383789062 5 WikiText2
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6287 = = = Databases and projects = = =
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179.63243103027344 9 WikiText2
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6288 The Protein Naming Utility
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3110.508544921875 4 WikiText2
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6289 Human Protein Atlas
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5165.125 3 WikiText2
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6290 NCBI Entrez Protein database
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2638.273681640625 4 WikiText2
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6291 NCBI Protein Structure database
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6264.8515625 4 WikiText2
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6292 Human Protein Reference Database
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1620.1978759765625 4 WikiText2
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6293 Human Proteinpedia
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30612.115234375 2 WikiText2
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6294 Folding @ Home ( Stanford University )
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501.1223449707031 7 WikiText2
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6295 Comparative Toxicogenomics Database curates protein – chemical interactions , as well as gene / protein – disease relationships and chemical @-@ disease relationships .
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371.3191223144531 26 WikiText2
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6296 Bioinformatic Harvester A Meta search engine ( 29 databases ) for gene and protein information .
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237.82696533203125 16 WikiText2
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6297 Protein Databank in Europe ( see also PDBeQuips , short articles and tutorials on interesting PDB structures )
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403.7005310058594 18 WikiText2
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6298 Research Collaboratory for Structural Bioinformatics ( see also Molecule of the Month , presenting short accounts on selected proteins from the PDB )
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167.95111083984375 23 WikiText2
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6299 Proteopedia – Life in 3D : rotatable , zoomable 3D model with wiki annotations for every known protein molecular structure .
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