Sunday, September 23, 2012

The primary structure of a protein

The primary structure of a protein is determined by the gene corresponding to the protein. A specific sequence of nucleotides in DNA is transcribed into mRNA, which is read by the ribosome in a process called translation. The sequence of a protein is unique to that protein, and defines the structure and function of the protein. Sony VGP-BPS13AS Battery
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 thegenetic code. We know that there are over 10,000 proteins in our body which are composed of different arrangements of 20 types of amino acid residues Sony VGP-BPS13B/B Battery
(it is strictly recommended to use the word "amino acid residues" as when peptide bond is formed a water molecule is lost so, protein is made up of amino acid residues) Post-translational modifications such as disulfide formation, phosphorylations and glycosylations are usually also considered a part of the primary structure, and cannot be read from the gene. Sony VGP-BPS13B/S Battery
Each α-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 different groups it is chiral, however only one of the isomers occur in biological proteins. Sony VGP-BPS13S Battery
Glycine however, is not chiral since its side chain is a hydrogen atom. A simple mnemonic for correct L-form is "CORN": when the Cα atom is viewed with the H in front, the residues read "CO-R-N" in a clockwise direction.
Secondary structure refers to highly regular local sub-structures. Sony VGP-BPS14 Battery
Two main types of secondary structure, the alpha helix and the beta strandor beta sheets, were suggested in 1951 by Linus Pauling and coworkers.[2] These secondary structures are defined by patterns of hydrogen bondsbetween the main-chain peptide groups. They have a regular geometry, Sony VGP-BPS14/B Battery
being constrained to specific values of the dihedral angles ψ and φ on the Ramachandran plot. Both the alpha helix and the beta-sheet represent a way of saturating all the hydrogen bond donors and acceptors in the peptide backbone. Some parts of the protein are ordered but do not form any regular structures. Sony VGP-BPS14/S Battery
They should not be confused with random coil, an unfolded polypeptide chain lacking any fixed three-dimensional structure. Several sequential secondary structures may form a "supersecondary unit".
Tertiary structure refers to three-dimensional structure of a single protein molecule. Sony VGP-BPS14B Battery
The alpha-helices and beta-sheets are folded into a compact globule. The folding is driven by the non-specific 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 specific tertiary interactions, such as salt bridges, Sony VGP-BPS15 Battery
hydrogen bonds, and the tight packing of side chains and disulfide bonds. The disulfide bonds are extremely rare in cytosolic proteins, since the cytosol is generally a reducing environment.
Tertiary structure refers to three-dimensional structure of a single protein molecule. The alpha-helices and beta-sheets are folded into a compact globule. Sony VGP-BPS15/S Battery
The folding is driven by the non-specific 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 specific tertiary interactions, such as salt bridges, hydrogen bonds, and the tight packing of side chains and disulfide bonds. Sony VGP-BPS18 Battery
The disulfide bonds are extremely rare in cytosolic proteins, since the cytosol is generally a reducing environment.
Protein are frequently described as consisting from several structural units.
structural domain is an element of the protein's overall structure that is self-stabilizing and often foldsindependently of the rest of the protein chain. Sony Vaio VGN-FZ Battery
Many domains are not unique to the protein products of one gene or onegene family but instead appear in a variety of proteins. Domains often are named and singled out because they figure prominently in the biological function of the protein they belong to; for example, the "calcium-binding domain ofcalmodulin". Sony Vaio VGN-FZ140E Battery
Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeras.
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.Sony Vaio VGN-FZ140E/B Battery
The supersecondary structure refers to a specific combination of secondary structure elements, such as beta-alpha-beta units or helix-turn-helix motif. Some of them may be also referred to as structural motifs.
Protein fold refers to the general protein architecture, like helix bundle, beta-barrel, Sony Vaio VGN-FZ11S Battery
Rossman fold or different "folds" provided in the Structural Classification of Proteins database.[4]
Despite the fact that there are about 100,000 different proteins expressed in eukaryotic systems, there are many fewer different domains, structural motifs and folds. Sony Vaio VGN-FZ11L Battery
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 3D density distribution of electrons in the protein (in the crystallized state) and thereby infer the 3D coordinates of all the atoms to be determined to a certain resolution. Sony Vaio VGN-FZ11M Battery
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 . Cryo-electron microscopy has recently become a means of determining protein structures to high resolution (less than 5 angstroms or 0.5 nanometer) Sony Vaio VGN-FZ11E Battery
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 complexes such as virus coat proteins and amyloid fibers.
The generation of a protein sequence is much easier than the determination of a protein structure. Sony Vaio VGN-FZ11Z Battery
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.[7] Ab initio prediction methods use just the sequence of the protein. Sony Vaio VGN-FZ140N Battery
Threading and Homology Modeling methods can build a 3D model for a protein of unknown structure from experimental structures of evolutionary related proteins.
Protein structure prediction is the prediction of the three-dimensional structure of a protein from its amino acid sequence — that is, the prediction of its secondary, tertiary, and quaternary structure from its primary structure. Sony Vaio VGN-FZ145E Battery
Structure prediction is fundamentally different from the inverse problem ofprotein design. Protein structure prediction is one of the most important goals pursued by bioinformatics and theoretical chemistry; it is highly important inmedicine (for example, in drug design) and biotechnology (for example, in the design of novel enzymes). Sony Vaio VGN-FZ15 Battery
Every two years, the performance of current methods is assessed in the CASP experiment (Critical Assessment of Techniques for Protein Structure Prediction).
Proteins are chains of amino acids joined together by peptide bonds. Many conformations of this chain are possible due to the rotation of the chain about each Cα atom. Sony Vaio VGN-FZ150E Battery
It is these informational changes that are responsible for differences in the three dimensional structure of proteins. Each amino acid in the chain is polar, i.e. it has separated positive and negative charged regions with a free C=O group, which can act as hydrogen bond acceptor and an NH group, which can act as hydrogen bond donor. Sony Vaio VGN-FZ150E-BC Battery
These groups can therefore interact in the protein structure. The 20 amino acids can be classified according to the chemistry of the side chain which also plays an important structural role. Glycine takes on a special position, as it does not have a side chain and therefore can increase the local flexibility in the protein structure. Sony Vaio VGN-FZ15G Battery
Cysteine on the other hand can react with another cysteine residue and thereby form a cross link stabilizing the whole structure.
The protein structure can be considered as a sequence of secondary structure elements, such as α helices and β sheets, which together constitute the overall three-dimensional configuration of the protein chain. Sony Vaio VGN-FZ15L Battery
In these secondary structures regular patterns of H bonds are formed between neighboring amino acids, and the amino acids have similar Φ and Ψ angles.
The formation of these structures neutralizes the polar groups on each amino acid. The secondary structures are tightly packed in the protein core in a hydrophobic environment. Sony Vaio VGN-FZ15M Battery
Each amino acid side group has a limited volume to occupy and a limited number of possible interactions with other near- by side chains, a situation that must be taken into account in molecular modeling and alignments.
The α helix is the most abundant type of secondary structure in proteins. Sony Vaio VGN-FZ15S Battery
The α helix has 3.6 amino acids per turn with an H bond formed between every fourth residue; the average length is 10 amino acids (3 turns) or 10 Å but varies from 5 to 40 (1.5 to 11 turns). The alignment of the H bonds creates a dipole moment for the helix with a resulting partial positive charge at the amino end of the helix. Sony Vaio VGN-FZ15T Battery
Because this region has free NH2 groups, it will interact with negatively charged groups such as phosphates. The most common location of α helices is at the surface of protein cores, where they provide an interface with the aqueous environment. The inner-facing side of the helix tends to have hydrophobic amino acids and the outer-facing side hydrophilic amino acids. Sony Vaio VGN-FZ18 Battery
Thus, every third of four amino acids along the chain will tend to be hydrophobic, a pattern that can be quite readily detected. In the leucine zipper motif, a repeating pattern of leucines on the facing sides of two adjacent helices is highly predictive of the motif. A helical-wheel plot can be used to show this repeated pattern. Sony Vaio VGN-FZ18E Battery
Other α helices buried in the protein core or in cellular membranes have a higher and more regular distribution of hydrophobic amino acids, and are highly predictive of such structures. Helices exposed on the surface have a lower proportion of hydrophobic amino acids. Amino acid content can be predictive of an α -helical region. Sony Vaio VGN-FZ18M Battery
Regions richer in alanine (A), glutamic acid (E), leucine (L), and methionine (M) and poorer in proline (P), glycine (G), tyrosine (Y), and serine (S) tend to form an α helix. Proline destabilizes or breaks an α helix but can be present in longer helices, forming a bend. There are computer programs for predicting quite reliably the general location of α helices in a new protein sequence. Sony Vaio VGN-FZ18L Battery
β Sheets are formed by H bonds between an average of 5–10 consecutive amino acids in one portion of the chain with another 5–10 farther down the chain. The interacting regions may be adjacent, with a short loop in between, or far apart, with other structures in between. Sony Vaio VGN-FZ18G Battery
Every chain may run in the same direction to form a parallel sheet, every other chain may run in the reverse chemical direction to form an anti parallel sheet, or the chains may be parallel and anti parallel to form a mixed sheet.The pattern of H bonding is different in the parallel and anti parallel configurations. Sony Vaio VGN-FZ18S Battery
Each amino acid in the interior strands of the sheet forms two H bonds with neighboring amino acids, whereas each amino acid on the outside strands forms only one bond with an interior strand. Looking across the sheet at right angles to the strands, more distant strands are rotated slightly counterclockwise to form a left-handed twist. Sony Vaio VGN-FZ460E Battery
The Cα atoms alternate above and below the sheet in a pleated structure, and the R side groups of the amino acids alternate above and below the pleats. The Φ and Ψ angles of the amino acids in sheets vary considerably in one region of the Ramachandran plot. It is more difficult to predict the location of β sheets than of α helices. Sony Vaio VGN-FZ21 Battery
The situation improves some what when the amino acid variation in multiple sequence alignments is taken into account.
Loops are regions of a protein chain that are (1) between α helices and β sheets, (2) of various lengths and three-dimensional configurations, and (3) on the surface of the structure. Sony Vaio VGN-FZ21M Battery
Hairpin loops that represent a complete turn in the polypeptide chain joining two antiparallel β strands may be as short as two amino acids in length. Loops interact with the surrounding aqueous environment and other proteins. Because amino acids in loops are not constrained by space and environment as are amino acids in the core region, Sony Vaio VGN-FZ21E Battery
and do not have an effect on the arrangement of secondary structures in the core, more substitutions, insertions, and deletions may occur. Thus, in a sequence alignment, the presence of these features may be an indication of a loop. The positions of introns in genomic DNA sometimes correspond to the locations of loops in the encoded protein. Sony Vaio VGN-FZ21S Battery
Loops also tend to have charged and polar amino acids and are frequently a component of active sites. A detailed examination of loop structures has shown that they fall into distinct families.
Proteins may be classified according to both structural and sequence similarity. Sony Vaio VGN-FZ21J Battery
For structural classification, the sizes and spatial arrangements of secondary structures described in the above paragraph are compared in known three-dimensional structures.Classification based on sequence similarity was historically the first to be used. Initially, similarity based on alignments of whole sequences was performed. Sony Vaio VGN-FZ21Z Battery
Later, proteins were classified on the basis of the occurrence of conserved amino acid patterns. Databases that classify proteins by one or more of these schemes are available. In considering protein classification schemes, it is important to keep several observations in mind. Sony Vaio VGN-FZ25 Battery
First, two entirely different protein sequences from different evolutionary origins may fold into a similar structure. Conversely, the sequence of an ancient gene for a given structure may have diverged considerably in different species while at the same time maintaining the same basic structural features. Sony Vaio VGN-FZ31E Battery
Recognizing any remaining sequence similarity in such cases may be a very difficult task. Second, two proteins that share a significant degree of sequence similarity either with each other or with a third sequence also share an evolutionary origin and should share some structural features also. Sony Vaio VGN-FZ31M Battery
However, gene duplication and genetic rearrangements during evolution may give rise to new gene copies, which can then evolve into proteins with new function and structure.
The more commonly used terms for describing evolutionary and structural relationships among proteins are listed below. Sony Vaio VGN-FZ31S Battery
Many additional terms are used to describe various kinds of structural features found in proteins. Descriptions of such terms may be found at the CATH Web site the Structural Classification of Proteins (SCOP) Web site and a Glaxo-Wellcome tutorial on the Swiss bioinformatics Expasy Web site. Sony Vaio VGN-FZ31J Battery
active site
a localized combination of amino acid side groups within the tertiary (three-dimensional) or quaternary (protein subunit) structure that can interact with a chemically specific substrate and that provides the protein with biological activity. Proteins of very different amino acid sequences may fold into a structure that produces the same active site. Sony Vaio VGN-FZ31B Battery
describes the relative orientations of secondary structures in a three-dimensional structure without regard to whether or not they share a similar loop structure.
a type of architecture that also has a conserved loop structure. Sony Vaio VGN-FZ32B Battery
a term used to describe a conserved amino acid sequence pattern in a family of proteins. The pattern includes a series of possible matches at each position in the rep- resented sequences, but there are not any inserted or deleted positions in the pattern or in the sequences. Sony Vaio VGN-FZ32 Battery
By way of contrast, sequence profiles are a type of scoring matrix that represents a similar set of patterns that includes insertions and deletions.
a term used to classify protein domains according to their secondary structural content and organization. Sony Vaio VGN-FZ38M Battery
Four classes were originally recognized by Levitt and Chothia (1976), and several others have been added in the SCOP database. Three classes are given in the CATH database: mainly-α, mainly-β, and α–β, with the α–β class including both alternating α /Β and α+β structures. Sony VAIO VGN-SR51MF/S Battery
the portion of a folded protein molecule that comprises the hydrophobic interior of α-helices and β-sheets. Sony Vaio VGN-FZ31Z Battery
The compact structure brings together side groups of amino acids into close enough proximity so that they can interact. When comparing protein structures, as in the SCOP database, core refers to the region common to most of the structures that share a common fold or that are in the same superfamily. Sony Vaio VGN-FW11 Battery
In structure prediction, core is sometimes defined as the arrangement of secondary structures that is likely to be conserved during evolutionary change.
domain (sequence context)
refers to a segment of a polypeptide chain that can fold into a three-dimensional structure irrespective of the presence of other segments of the chain. Sony Vaio VGN-FW11M Battery
The separate domains of a given protein may interact extensively or may be joined only by a length of polypeptide chain. A protein with several domains may use these domains for functional interactions with different molecules.
family (sequence context)
a group of proteins of similar biochemical function that are more than 50% identical when aligned. Sony Vaio VGN-FW11S Battery

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