Structural motif

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.

Johansson, M.U. (23 July 2012). “Defining and searching for structural motifs using DeepView/Swiss-PdbViewer”. BMC Bioinformatics. 13 (173): 173. doi:10.1186/1471-2105-13-173. PMC 3436773. PMID 22823337.

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.

In nucleic acids

See also: Non-B database

This section needs expansion. You can help by adding to it. (August 2020)

Depending upon the sequence and other conditions, nucleic acids can form a variety of structural motifs which is thought to have biological significance.

Stem-loop
- Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded DNA or, more commonly, in RNA.
  - ^{Bolshoy, Alexander (2010). Genome Clustering: From Linguistic Models to Classification of Genetic Texts. Springer. p. 47. ISBN 9783642129513. Retrieved 24 March 2021.}
- The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions, base-pair to form a double helix that ends in an unpaired loop. The resulting structure is a key building block of many RNA secondary structures.
Cruciform DNA
- Cruciform DNA is a form of non-B DNA that requires at least a 6 nucleotide sequence of inverted repeats to form a structure consisting of a stem, branch point and loop in the shape of a cruciform, stabilized by negative DNA supercoiling.
  - ^{Shlyakhtenko LS, Potaman VN, Sinden RR, Lyubchenko YL (July 1998). “Structure and dynamics of supercoil-stabilized DNA cruciforms”. J. Mol. Biol. 280 (1): 61–72. CiteSeerX 10.1.1.555.4352. doi:10.1006/jmbi.1998.1855. PMID 9653031.}
- Two classes of cruciform DNA have been described; folded and unfolded.
G-quadruplex
- G-quadruplexsecondary structures (G4) are formed in nucleic acids by sequences that are rich in guanine.
  - ^{Routh ED, Creacy SD, Beerbower PE, Akman SA, Vaughn JP, Smaldino PJ (March 2017). “A G-quadruplex DNA-affinity Approach for Purification of Enzymaticacvly Active G4 Resolvase1”. Journal of Visualized Experiments. 121 (121). doi:10.3791/55496. PMC 5409278. PMID 28362374.}
- They are helical in shape and contain guanine tetrads that can form from one, two or four strands.
  - Largy E, Mergny J, Gabelica V (2016). “Chapter 7. Role of Alkali Metal Ions in G-Quadruplex Nucleic Acid Structure and Stability”. In Astrid S, Helmut S, Roland KO S (eds.). The Alkali Metal Ions: Their Role in Life (PDF). Metal Ions in Life Sciences. Vol. 16. Springer. pp. 203–258. doi:10.1007/978-3-319-21756-7_7. PMID 26860303.
  - Sundquist WI, Klug A (December 1989). “Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops”. Nature. 342 (6251): 825–9. Bibcode:1989Natur.342..825S. doi:10.1038/342825a0. PMID 2601741. S2CID 4357161.
  - Sen D, Gilbert W (July 1988). “Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis”. Nature. 334 (6180): 364–6. Bibcode:1988Natur.334..364S. doi:10.1038/334364a0. PMID 3393228. S2CID 4351855.

D-loop
- A displacement loop or D-loop is a DNA structure where the two strands of a double-stranded DNA molecule are separated for a stretch and held apart by a third strand of DNA.
  - ^{DePamphilis, Melvin (2011). Genome Duplication. Garland Science, Taylor & Francis Group, LLC. p. 419. ISBN 9780415442060. Retrieved 24 March 2021.}
- An R-loop is similar to a D-loop, but in this case the third strand is RNA rather than DNA.
  - ^{Al-Hadid, Qais (July 1, 2016). “R-loop: an emerging regulator of chromatin dynamics”. Acta Biochim Biophys Sin (Shanghai). 48 (7): 623–31. doi:10.1093/abbs/gmw052. PMC 6259673. PMID 27252122.}
- The third strand has a base sequence which is complementary to one of the main strands and pairs with it, thus displacing the other complementary main strand in the region. Within that region the structure is thus a form of triple-stranded DNA. A diagram in the paper introducing the term illustrated the D-loop with a shape resembling a capital “D”, where the displaced strand formed the loop of the “D”.
  - ^{Kasamatsu, H.; Robberson, D. L.; Vinograd, J. (1971). “A novel closed-circular mitochondrial DNA with properties of a replicating intermediate”. Proceedings of the National Academy of Sciences of the United States of America. 68 (9): 2252–2257. Bibcode:1971PNAS…68.2252K. doi:10.1073/pnas.68.9.2252. PMC 389395. PMID 5289384.}

In proteins

In proteins, a structural motif describes the connectivity between secondary structural elements. An individual motif usually consists of only a few elements, e.g., the ‘helix-turn-helix’ motif which has just three. Note that, while the spatial sequence of elements may be identical in all instances of a motif, they may be encoded in any order within the underlying gene. In addition to secondary structural elements, protein structural motifs often include loops of variable length and unspecified structure. Structural motifs may also appear as tandem repeats.

Beta hairpin
- Extremely common. Two antiparallel beta strands connected by a tight turn of a few amino acids between them.

Greek key
- Four beta strands, three connected by hairpins, the fourth folded over the top.
Omega loop
- A loop in which the residues that make up the beginning and end of the loop are very close together.
  - ^{Hettiarachchy, Navam S (2012). Food Proteins and Peptides: Chemistry, Functionality, Interactions, and Commercialization. CRC Press Taylor & Francis Group. p. 16. ISBN 9781420093421. Retrieved 24 March 2021.}
Helix-loop-helix
- Consists of alpha helices bound by a looping stretch of amino acids. This motif is seen in transcription factors.
Zinc finger
- Two beta strands with an alpha helix end folded over to bind a zinc ion. Important in DNA binding proteins.
Helix-turn-helix
- Two α helices joined by a short strand of amino acids and found in many proteins that regulate gene expression.
  - ^{Dubey, R C (2014). Advanced Biotechnology. S Chand Publishing. p. 505. ISBN 978-8121942904. Retrieved 24 March 2021.}
Nest
- Extremely common. Three consecutive amino acid residues form an anion-binding concavity.
  - ^{Milner-White, E. James (September 26, 2011). “Functional Capabilities of the Earliest Peptides and the Emergence of Life”. Genes. 2 (4): 674. doi:10.3390/genes2040671. PMC 3927598. PMID 24710286.}
Niche
- Extremely common. Three or four consecutive amino acid residues form a cation-binding feature.
  - ^{Milner-White, E. James (September 26, 2011). “Functional Capabilities of the Earliest Peptides and the Emergence of Life”. Genes. 2 (4): 678. doi:10.3390/genes2040671. PMC 3927598. PMID 24710286.}