Trình tự motif

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Một trình tự motif là một đoạn trình tự nucleotide hoặc amino acid phổ biến và có, hoặc cho là có, một chức năng sinh học nào đó.

Ví dụ như motif về vị trí gắn thêm gốc N-glycosyl:

Asn, tiếp đến là bất kỳ a.a nào trừ Pro, tiếp đến là Ser hoặc Thr, sau đó có thể là bất kỳ a.a nào trừ Pro

trong đó chữ viết tắt là ký hiệu cho các amino acid theo kiểu viết tắt 3 chữ cái, (xem mã di truyền).

[sửa] Tổng quan

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.

[sửa] Tin sinh học về motif

Consider the N-glycosylation site motif mentioned above:

Asn, followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro

This pattern may be written as N{P}[ST]{P} where N=Asn, P=Pro, S=Ser, T=Thr; {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.

[sửa] Các motif và trình tự bảo thủ (consensus sequences)

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:

[FILV]Qxxx[RK]Gxxx[RK]xx[FILVWY]

where x signifies any amino acid, and the square brackets indicate an alternative (see below for further details about notation).

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.

[sửa] Phần mềm

There are software programs which, given multiple input sequences, attempt to identify one or more candidate motifs. One example is MEME, which generates statistical information for each candidate.

[sửa] Discovery through evolutionary conservation

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:

WDIND*.*P..*...D.F.*W***.**.IYS**...A.*H*S*WAMRNTNNHN

Here each . signifies a single amino acid or a gap, and each * indicates one member of a closely-related family of amino acids.

The authors were able to show that the motif has DNA binding activity.

[sửa] Pattern description notations

Several notations for describing motifs are in use but most of them are variants of standard notations for regular expressions and use these conventions:

there is an alphabet of single characters, each denoting a specific amino acid or a set of amino acids;
a string of characters drawn from the alphabet denotes a sequence of the corresponding amino acids;
any string of characters drawn from the alphabet enclosed in square brackets matches any one of the corresponding amino acids; e.g. [abc] matches any of the amino acids represented by a or b or c.

The fundamental idea behind all these notations is the matching principle, which assigns a meaning to a sequence of elements of the pattern notation:

a sequence of elements of the pattern notation matches a sequence of amino acids if and only if the latter sequence can be partitioned into subsequences in such a way that each pattern element matches the corresponding subsequence in turn.

Thus the pattern [AB] [CDE] F matches the six amino acid sequences corresponding to ACF, ADF, AEF, BCF, BDF, and BEF.

Different pattern description notations have other ways of forming pattern elements. One of these notations is the PROSITE notation, described in the following subsection.

[sửa] PROSITE pattern notation

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:

The lower case letter 'x' can be used as a pattern element to denote any amino acid.
A string of characters drawn from the alphabet and enclosed in braces (curly brackets) denotes any amino acid except for those in the string. For example, {ST} denotes any amino acid other than S or T.
If a pattern is restricted to the N-terminal of a sequence, the pattern is prefixed with '<'.
If a pattern is restricted to the C-terminal of a sequence, the pattern is suffixed with '>'.
The character '>' can also occur inside a terminating square bracket pattern, so that S[T>] matches both "ST" and "S>".
If e is a pattern element, and m and n are two decimal integers with m <= n, then:
- e(m) is equivalent to the repetition of e exactly m times;
- e(m,n) is equivalent to the repetition of e exactly k times for any integer k satisfying: m <= k <= n.

Some examples:

x(3) is equivalent to x-x-x.
x(2,4) matches any sequence that matches x-x or x-x-x or x-x-x-x.

The signature of the C2H2-type zinc finger domain is:

C-x(2,4)-C-x(3)-[LIVMFYWC]-x(8)-H-x(3,5)-H

[sửa] Another scheme

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:

	3D chain code	Amino acid sequence
1lccA	`TWWWWWWWKCLKWWWWWWG`	`LYDVAEYAGVSYQTVSRVV`
3gapA	`KWWWWWWGKCFKWWWWWWW`	`RQEIGQIVGCSRETVGRIL`

[sửa] Tài liệu tham khảo

Akiyama, Y. et al. (1996). The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Proc. Natl. Acad. Sci. USA 93 14912–14916.
Matsuda, Hideo; Taniguchi, Fumihiro; & Hashimoto, Akihiro (January 1997). An Approach to Detection of Protein Structural Motifs using an Encoding Scheme of Backbone Conformations. Proc. of 2nd Pacific Symposium on Biocomputing 280–291.

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