Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary, and quaternary.
Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary, and quaternary.
Primary structure consists of a linear sequence of nucleotides that are linked together by phosphodiester bonds. It is this linear sequence of nucleotides that make up the primary structure of DNA or RNA. Nucleotides consist of 3 components:
The nitrogen bases adenine and guanine are purine in structure and form a glycosidic bond between their 9 nitrogen and the 1' -OH group of the deoxyribose. Cytosine, thymine, and uracil are pyrimidines, hence the glycosidic bonds form between their 1 nitrogen and the 1' -OH of the deoxyribose. For both the purine and pyrimidine bases, the phosphate group forms a bond with the deoxyribose sugar through an ester bond between one of its negatively charged oxygen groups and the 5' -OH of the sugar. [2] The polarity in DNA and RNA is derived from the oxygen and nitrogen atoms in the backbone. Nucleic acids are formed when nucleotides come together through phosphodiester linkages between the 5' and 3' carbon atoms. [3] A nucleic acid sequence is the order of nucleotides within a DNA (GACT) or RNA (GACU) molecule that is determined by a series of letters. Sequences are presented from the 5' to 3' end and determine the covalent structure of the entire molecule. Sequences can be complementary to another sequence in that the base on each position is complementary as well as in the reverse order. An example of a complementary sequence to AGCT is TCGA. DNA is double-stranded containing both a sense strand and an antisense strand. Therefore, the complementary sequence will be to the sense strand. [4]
There are three potential metal binding groups on nucleic acids: phosphate, sugar, and base moieties. Solid-state structure of complexes with alkali metal ions have been reviewed. [6]
Secondary structure is the set of interactions between bases, i.e., which parts of strands are bound to each other. In DNA double helix, the two strands of DNA are held together by hydrogen bonds. The nucleotides on one strand base pairs with the nucleotide on the other strand. The secondary structure is responsible for the shape that the nucleic acid assumes. The bases in the DNA are classified as purines and pyrimidines. The purines are adenine and guanine. Purines consist of a double ring structure, a six-membered and a five-membered ring containing nitrogen. The pyrimidines are cytosine and thymine. It has a single ring structure, a six-membered ring containing nitrogen. A purine base always pairs with a pyrimidine base (guanine (G) pairs with cytosine (C) and adenine (A) pairs with thymine (T) or uracil (U)). DNA's secondary structure is predominantly determined by base-pairing of the two polynucleotide strands wrapped around each other to form a double helix. Although the two strands are aligned by hydrogen bonds in base pairs, the stronger forces holding the two strands together are stacking interactions between the bases. These stacking interactions are stabilized by Van der Waals forces and hydrophobic interactions, and show a large amount of local structural variability. [7] There are also two grooves in the double helix, which are called major groove and minor groove based on their relative size.
The secondary structure of RNA consists of a single polynucleotide. Base pairing in RNA occurs when RNA folds between complementarity regions. Both single- and double-stranded regions are often found in RNA molecules.
The four basic elements in the secondary structure of RNA are:
The antiparallel strands form a helical shape. [3] Bulges and internal loops are formed by separation of the double helical tract on either one strand (bulge) or on both strands (internal loops) by unpaired nucleotides.
Stem-loop or hairpin loop is the most common element of RNA secondary structure. [8] Stem-loop is formed when the RNA chains fold back on themselves to form a double helical tract called the 'stem', the unpaired nucleotides forms single stranded region called the 'loop'. A tetraloop is a four-base pairs hairpin RNA structure. There are three common families of tetraloop in ribosomal RNA: UNCG, GNRA, and CUUG (N is one of the four nucleotides and R is a purine). UNCG is the most stable tetraloop. [9]
Pseudoknot is an RNA secondary structure first identified in turnip yellow mosaic virus. [10] It is minimally composed of two helical segments connected by single-stranded regions or loops. H-type fold pseudoknots are best characterized. In H-type fold, nucleotides in the hairpin-loop pair with the bases outside the hairpin stem forming second stem and loop. This causes formation of pseudoknots with two stems and two loops. [11] Pseudoknots are functional elements in RNA structure having diverse function and found in most classes of RNA.
Secondary structure of RNA can be predicted by experimental data on the secondary structure elements, helices, loops, and bulges. DotKnot-PW method is used for comparative pseudoknots prediction. The main points in the DotKnot-PW method is scoring the similarities found in stems, secondary elements and H-type pseudoknots. [12]
Tertiary structure refers to the locations of the atoms in three-dimensional space, taking into consideration geometrical and steric constraints. It is a higher order than the secondary structure, in which large-scale folding in a linear polymer occurs and the entire chain is folded into a specific 3-dimensional shape. There are 4 areas in which the structural forms of DNA can differ.
The tertiary arrangement of DNA's double helix in space includes B-DNA, A-DNA, and Z-DNA. Triple-stranded DNA structures have been demonstrated in repetitive polypurine:polypyrimidine Microsatellite sequences and Satellite DNA.
B-DNA is the most common form of DNA in vivo and is a more narrow, elongated helix than A-DNA. Its wide major groove makes it more accessible to proteins. On the other hand, it has a narrow minor groove. B-DNA's favored conformations occur at high water concentrations; the hydration of the minor groove appears to favor B-DNA. B-DNA base pairs are nearly perpendicular to the helix axis. The sugar pucker which determines the shape of the a-helix, whether the helix will exist in the A-form or in the B-form, occurs at the C2'-endo. [13]
A-DNA, is a form of the DNA duplex observed under dehydrating conditions. It is shorter and wider than B-DNA. RNA adopts this double helical form, and RNA-DNA duplexes are mostly A-form, but B-form RNA-DNA duplexes have been observed. [14] In localized single strand dinucleotide contexts, RNA can also adopt the B-form without pairing to DNA. [15] A-DNA has a deep, narrow major groove which does not make it easily accessible to proteins. On the other hand, its wide, shallow minor groove makes it accessible to proteins but with lower information content than the major groove. Its favored conformation is at low water concentrations. A-DNAs base pairs are tilted relative to the helix axis, and are displaced from the axis. The sugar pucker occurs at the C3'-endo and in RNA 2'-OH inhibits C2'-endo conformation. [13] Long considered little more than a laboratory artifice, A-DNA is now known to have several biological functions.
Z-DNA is a relatively rare left-handed double-helix. Given the proper sequence and superhelical tension, it can be formed in vivo but its function is unclear. It has a more narrow, more elongated helix than A or B. Z-DNA's major groove is not really a groove, and it has a narrow minor groove. The most favored conformation occurs when there are high salt concentrations. There are some base substitutions but they require an alternating purine-pyrimidine sequence. The N2-amino of G H-bonds to 5' PO, which explains the slow exchange of protons and the need for the G purine. Z-DNA base pairs are nearly perpendicular to the helix axis. Z-DNA does not contain single base-pairs but rather a GpC repeat with P-P distances varying for GpC and CpG. On the GpC stack there is good base overlap, whereas on the CpG stack there is less overlap. Z-DNA's zigzag backbone is due to the C sugar conformation compensating for G glycosidic bond conformation. The conformation of G is syn, C2'-endo; for C it is anti, C3'-endo. [13]
A linear DNA molecule having free ends can rotate, to adjust to changes of various dynamic processes in the cell, by changing how many times the two chains of its double helix twist around each other. Some DNA molecules are circular and are topologically constrained. More recently circular RNA was described as well to be a natural pervasive class of nucleic acids, expressed in many organisms (see CircRNA).
A covalently closed, circular DNA (also known as cccDNA) is topologically constrained as the number of times the chains coiled around one other cannot change. This cccDNA can be supercoiled, which is the tertiary structure of DNA. Supercoiling is characterized by the linking number, twist and writhe. The linking number (Lk) for circular DNA is defined as the number of times one strand would have to pass through the other strand to completely separate the two strands. The linking number for circular DNA can only be changed by breaking of a covalent bond in one of the two strands. Always an integer, the linking number of a cccDNA is the sum of two components: twists (Tw) and writhes (Wr). [16]
Twists are the number of times the two strands of DNA are twisted around each other. Writhes are number of times the DNA helix crosses over itself. DNA in cells is negatively supercoiled and has the tendency to unwind. Hence the separation of strands is easier in negatively supercoiled DNA than in relaxed DNA. The two components of supercoiled DNA are solenoid and plectonemic. The plectonemic supercoil is found in prokaryotes, while the solenoidal supercoiling is mostly seen in eukaryotes.
The quaternary structure of nucleic acids is similar to that of protein quaternary structure. Although some of the concepts are not exactly the same, the quaternary structure refers to a higher-level of organization of nucleic acids. Moreover, it refers to interactions of the nucleic acids with other molecules. The most commonly seen form of higher-level organization of nucleic acids is seen in the form of chromatin which leads to its interactions with the small proteins histones. Also, the quaternary structure refers to the interactions between separate RNA units in the ribosome or spliceosome. [17]
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, "Watson–Crick" base pairs allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence. The complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. The regular structure and data redundancy provided by the DNA double helix make DNA well suited to the storage of genetic information, while base-pairing between DNA and incoming nucleotides provides the mechanism through which DNA polymerase replicates DNA and RNA polymerase transcribes DNA into RNA. Many DNA-binding proteins can recognize specific base-pairing patterns that identify particular regulatory regions of genes.
Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.
Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is deoxyribose, a variant of ribose, the polymer is DNA.
Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.
An inverted repeat is a single stranded sequence of nucleotides followed downstream by its reverse complement. The intervening sequence of nucleotides between the initial sequence and the reverse complement can be any length including zero. For example, 5'---TTACGnnnnnnCGTAA---3' is an inverted repeat sequence. When the intervening length is zero, the composite sequence is a palindromic sequence.
Nucleotide bases are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Five nucleobases—adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)—are called primary or canonical. They function as the fundamental units of the genetic code, with the bases A, G, C, and T being found in DNA while A, G, C, and U are found in RNA. Thymine and uracil are distinguished by merely the presence or absence of a methyl group on the fifth carbon (C5) of these heterocyclic six-membered rings. In addition, some viruses have aminoadenine (Z) instead of adenine. It differs in having an extra amine group, creating a more stable bond to thymine.
In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have to be associated with a sequence motif; it can be represented by different and completely unrelated sequences in different proteins or RNA.
A Hoogsteen base pair is a variation of base-pairing in nucleic acids such as the A•T pair. In this manner, two nucleobases, one on each strand, can be held together by hydrogen bonds in the major groove. A Hoogsteen base pair applies the N7 position of the purine base and C4 amino group, which bind the Watson–Crick (N3–C4) face of the pyrimidine base.
Triple-stranded DNA is a DNA structure in which three oligonucleotides wind around each other and form a triple helix. In triple-stranded DNA, the third strand binds to a B-form DNA double helix by forming Hoogsteen base pairs or reversed Hoogsteen hydrogen bonds.
Stem-loops are nucleic acid secondary structural elements which form via intramolecular base pairing in single-stranded DNA or RNA. They are also referred to as hairpins or hairpin loops. A stem-loop occurs when two regions of the same nucleic acid strand, usually complementary in nucleotide sequence, base-pair to form a double helix that ends in a loop of unpaired nucleotides.
In molecular biology, the term double helix refers to the structure formed by double-stranded molecules of nucleic acids such as DNA. The double helical structure of a nucleic acid complex arises as a consequence of its secondary structure, and is a fundamental component in determining its tertiary structure. The structure was discovered by Maurice Wilkins, Rosalind Franklin, her student Raymond Gosling, James Watson, and Francis Crick, while the term "double helix" entered popular culture with the 1968 publication of Watson's The Double Helix: A Personal Account of the Discovery of the Structure of DNA.
Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length scales ranging from the level of individual atoms to the relationships among entire protein subunits. This useful distinction among scales is often expressed as a decomposition of molecular structure into four levels: primary, secondary, tertiary, and quaternary. The scaffold for this multiscale organization of the molecule arises at the secondary level, where the fundamental structural elements are the molecule's various hydrogen bonds. This leads to several recognizable domains of protein structure and nucleic acid structure, including such secondary-structure features as alpha helixes and beta sheets for proteins, and hairpin loops, bulges, and internal loops for nucleic acids. The terms primary, secondary, tertiary, and quaternary structure were introduced by Kaj Ulrik Linderstrøm-Lang in his 1951 Lane Medical Lectures at Stanford University.
DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled". The amount of a strand's supercoiling affects a number of biological processes, such as compacting DNA and regulating access to the genetic code. Certain enzymes, such as topoisomerases, change the amount of DNA supercoiling to facilitate functions such as DNA replication and transcription. The amount of supercoiling in a given strand is described by a mathematical formula that compares it to a reference state known as "relaxed B-form" DNA.
Nucleic acid tertiary structure is the three-dimensional shape of a nucleic acid polymer. RNA and DNA molecules are capable of diverse functions ranging from molecular recognition to catalysis. Such functions require a precise three-dimensional structure. While such structures are diverse and seemingly complex, they are composed of recurring, easily recognizable tertiary structural motifs that serve as molecular building blocks. Some of the most common motifs for RNA and DNA tertiary structure are described below, but this information is based on a limited number of solved structures. Many more tertiary structural motifs will be revealed as new RNA and DNA molecules are structurally characterized.
Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNAs and RNAs tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.
In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. In nature complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complementary base pairing allows cells to copy information from one generation to another and even find and repair damage to the information stored in the sequences.
Nucleic acid NMR is the use of nuclear magnetic resonance spectroscopy to obtain information about the structure and dynamics of nucleic acid molecules, such as DNA or RNA. It is useful for molecules of up to 100 nucleotides, and as of 2003, nearly half of all known RNA structures had been determined by NMR spectroscopy.
xDNA is a size-expanded nucleotide system synthesized from the fusion of a benzene ring and one of the four natural bases: adenine, guanine, cytosine, and thymine. This size expansion produces an 8 letter alphabet which has a larger information storage capacity than natural DNA's 4 letter alphabet. As with normal base-pairing, A pairs with xT, C pairs with xG, G pairs with xC, and T pairs with xA. The double helix is thus 2.4Å wider than a natural double helix. While similar in structure to B-DNA, xDNA has unique absorption, fluorescence, and stacking properties.
Non-canonical base pairs are planar hydrogen bonded pairs of nucleobases, having hydrogen bonding patterns which differ from the patterns observed in Watson-Crick base pairs, as in the classic double helical DNA. The structures of polynucleotide strands of both DNA and RNA molecules can be understood in terms of sugar-phosphate backbones consisting of phosphodiester-linked D 2’ deoxyribofuranose sugar moieties, with purine or pyrimidine nucleobases covalently linked to them. Here, the N9 atoms of the purines, guanine and adenine, and the N1 atoms of the pyrimidines, cytosine and thymine, respectively, form glycosidic linkages with the C1’ atom of the sugars. These nucleobases can be schematically represented as triangles with one of their vertices linked to the sugar, and the three sides accounting for three edges through which they can form hydrogen bonds with other moieties, including with other nucleobases. The side opposite to the sugar linked vertex is traditionally called the Watson-Crick edge, since they are involved in forming the Watson-Crick base pairs which constitute building blocks of double helical DNA. The two sides adjacent to the sugar-linked vertex are referred to, respectively, as the Sugar and Hoogsteen edges.
Non-B DNA refers to DNA conformations that differ from the canonical B-DNA conformation, the most common form of DNA found in nature at neutral pH and physiological salt concentrations. Non-B DNA structures can arise due to various factors, including DNA sequence, length, supercoiling, and environmental conditions. Non-B DNA structures can have important biological roles, but they can also cause problems, such as genomic instability and disease.
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