Sequence motif
A sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance.An example is the N-glycosylation site motif:
- Asn, followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro
When a sequence motif appears in the exon of a gene, it may encode the "structural motif" of a protein; that is a stereotypical element of the overall structure of the protein. Nevertheless, motifs need not be associated with a distinctive secondary structure. "Noncoding" sequences are not translated into proteins and nucleic acids with such motifs need not deviate from the typical shape (e.g. the "B-form" DNA double helix).
Outside of gene exons, there exist regulatory sequence motifs and motifs within the "junk," such as satellite DNA. Some of these are believed to affect the shape of nucleic acids (see for example RNA self-splicing), but this is only sometimes the case. For example, many DNA binding proteins that have affinities for specific motifs only bind DNA in its double-helical form. They are able to recognize motifs through contact with the double helix's major or minor groove.
Short coding motifs, which appear to lack secondary structure, include those that label proteins for delivery to particular parts of a cell, or mark them for phosphorylation.
Within a sequence or database of sequences, researchers search and find motifs using computer-based techniques of sequence analysis, such as BLAST. Such techniques belong to the discipline of bioinformatics.
See also: consensus sequence.
Consider the N-glycosylation site motif mentioned above:
where N=Asn, P=Pro, S=Ser, T=Thr
and {X} means any amino acid except X; and [XY] means either X or Y.
The notation [XY] does not give any indication of the probability of X or Y occurring in the pattern. Sometimes patterns are defined in terms of a probabilistic model such as a hidden Markov model.
The notation [XYZ] means X or Y or Z, but does not indicate the likelihood of
any particular match. For this reason, two or more patterns are often associated with a single motif - the defining pattern, and various typical patterns.
For example, the defining sequence for the IQ motif may be taken to be:
Usually, however, the first letter is I, and both [RK] choices resolve to R.
Since the last choice is so wide, the pattern IQxxxRGxxxR is sometimes
equated with the IQ motif itself, but a more accurate description would
be a consensus sequence for the IQ motif.
There are software programs which, given multiple input sequences, attempt to identify one or more candidate motifs. One example is MEME (see References below), which generates statistical information for each candidate.
Motifs have been discovered by studying similar genes in different species.
For example, by aligning the amino acid sequences specified by
the GCM (glial cells missing) gene in man, mouse and D. melanogaster,
Akiyama and others discovered a pattern which they called the GCM motif.
It spans about 150 amino acid residues, and begins as follows:
The authors were able to show that the motif has DNA binding activity.
Several notations for describing motifs are in use but
most of them are variants of standard notations for regular expressions
and use these conventions:
Different pattern description notations have other ways of forming pattern elements. One of these notations is the PROSITE notation, described in the following subsection.
The PROSITE notation uses the IUPAC one-letter codes and conforms to
the above description with the exception that a concatenation symbol, '-', is used between pattern elements, but it is often dropped between letters of the pattern alphabet.
PROSITE allows the following pattern elements in addition to those described previously:
This example comes from the paper by Matsuda and colleagues cited below.
The E. coli lactose operon repressor LacI (PDB id 1lccA) and E. coli catabolite gene activator (PDB id 3gapA) both have a helix-turn-helix motif, but their amino acid sequences do not show much similarity, as shown in the table below.
Matsuda and colleagues devised a code called the 3D chain code for
representing a protein structure as a string of letters. This encoding scheme reveals the similarity between the proteins much more clearly than the amino acid sequence:
Overview
Motif bioinformatics
This pattern may be written as N{P}[ST]{P}Motifs and consensus sequences
where x signifies any amino acid, and the square brackets indicate an alternative (see below for further details about notation).Software
Discovery through evolutionary conservation
Here each . signifies a single amino acid or a gap, and each * indicates
one member of a closely-related family of amino acids.Pattern Description Notations
The fundamental idea behind all these notations is the matching principle, which assigns a meaning to a sequence of elements of the pattern notation:
Thus the pattern [AB] [CDE] F matches the six amino acid sequences corresponding to ACF, ADF, AEF, BCF, BDF, and BEF.PROSITE Pattern Notation
Some examples:
The signature of the C2H2-type zinc finger domain is:
Another scheme
3D chain code Amino acid sequence 1lccA TWWWWWWWKCLKWWWWWWG LYDVAEYAGVSYQTVSRVV 3gapA KWWWWWWGKCFKWWWWWWW RQEIGQIVGCSRETVGRIL References