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PROSITE documentation PDOC50961

La-type HTH domain profile





Description

The La-type HTH domain is an RNA-binding, winged helix-turn-helix (wHTH) domain of about 90 residues present in La proteins and other eukaryotic RNA-binding proteins. The domain is named after human La protein, originally characterized as an autoantigen of the rheumatic diseases systemic lupus erythematosus and Sjogren's syndrome (La derives from the patient's name). La homologs have been found in all eukaryots including plants, trypanosomes and yeast. The La protein is a nuclear phosphoprotein that recognizes the 3' uridylates (3' UUU[OH]) present in all newly synthesized RNA polymerase III transcripts. La binding stabilizes these transcripts from exonucleases and may assist their folding. The La-type HTH domain occurs in the N-terminal part of La proteins, followed by one or two RNA recognition motifs (RRM) (see <PDOC00030>). The La-type HTH also occurs in combination with a double-stranded RNA binding motif and with a SAM binding motif.

The crystal structure of the N-terminal domain of the La protein from Trypanosoma brucei shows that the domain forms a wHTH containing six α-helices (H) and a three-stranded (B) antiparallel sheet with a topology H1-H1'-H2-B1-H3-H4-H5-B2-B3 (see <PDB:1S29>). The wHTH fold is found in eukaryotic and prokaryotic transcription factors, wherein the wHTH specifically binds to dsDNA (e.g. see <PDOC00042>). Two of the three N-terminal helices and helix 4 may be considered as insertions into such wHTH topologies. The helices 3 and 5 correspond with the HTH and the strands form the wing in such transcription factors, where these structures bind DNA. A different surface, which is formed by a conserved aromatic patch between helices H1, H1', H2 and the loop between H3 and H4 may bind RNA in the La-type HTH domain [1].

Some proteins known to contain a La-type HTH domain:

  • Eukaryotic La protein, a nuclear protein that binds the 3' termini of nascent RNA polymerase III transcripts and other small RNA, like pre-tRNA's, 5S rRNA's, U6 RNA and SRP RNA, as characterized in humans, fruit fly, baker's and fission yeast, and Trypanosoma brucei. Both the La-type HTH domain and the RRM are required for RNA binding by La. The aromatic patch of the La-type wHTH is required for specific binding to the 3'UUU[OH] of pre-tRNA [1,2].
  • Saccharomyces cerevisiae SRO9 and SLF1, which associate with polyribosomes and may function in translation.
  • Euplotes aediculatus p43, a component of the ciliate's telomerase ribonucleoprotein. P43 does not bind to the 3' UUU[OH].

The profile we developed covers the entire La-type HTH domain.

Note:

The La-type HTH domain has also been named LM for 'La motif' [1].

Last update:

March 2004 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

HTH_LA, PS50961; La-type HTH domain profile  (MATRIX)


References

1AuthorsDong G. Chakshusmathi G. Wolin S.L. Reinisch K.M.
TitleStructure of the La motif: a winged helix domain mediates RNA binding via a conserved aromatic patch.
SourceEMBO J. 23:1000-1007(2004).
PubMed ID14976553
DOI10.1038/sj.emboj.7600115

2AuthorsWolin S.L. Cedervall T.
TitleThe La protein.
SourceAnnu. Rev. Biochem. 71:375-403(2002).
PubMed ID12045101
DOI10.1146/annurev.biochem.71.090501.150003



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