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PMID: 17517123 Published · epublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors.

BMC genomics ·Vol. 8 ·2007-05-21 ·Pages 124

Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K, Kuroki Y

Abstract

Toll-like receptors (TLRs) play a central role in innate immunity. TLRs are membrane glycoproteins and contain leucine rich repeat (LRR) motif in the ectodomain. TLRs recognize and respond to molecules such as lipopolysaccharide, peptidoglycan, flagellin, and RNA from bacteria or viruses. The LRR domains in TLRs have been inferred to be responsible for molecular recognition. All LRRs include the highly conserved segment, LxxLxLxxNxL, in which "L" is Leu, Ile, Val, or Phe and "N" is Asn, Thr, Ser, or Cys and "x" is any amino acid. There are seven classes of LRRs including "typical" ("T") and "bacterial" ("S"). All known domain structures adopt an arc or horseshoe shape. Vertebrate TLRs form six major families. The repeat numbers of LRRs and their "phasing" in TLRs differ with isoforms and species; they are aligned differently in various databases. We identified and aligned LRRs in TLRs by a new method described here. The new method utilizes known LRR structures to recognize and align new LRR motifs in TLRs and incorporates multiple sequence alignments and secondary structure predictions. TLRs from thirty-four vertebrate were analyzed. The repeat numbers of the LRRs ranges from 16 to 28. The LRRs found in TLRs frequently consists of LxxLxLxxNxLxxLxxxxF/LxxLxx ("T") and sometimes short motifs including LxxLxLxxNxLxxLPx(x)LPxx ("S"). The TLR7 family (TLR7, TLR8, and TLR9) contain 27 LRRs. The LRRs at the N-terminal part have a super-motif of STT with about 80 residues. The super-repeat is represented by STTSTTSTT or _TTSTTSTT. The LRRs in TLRs form one or two horseshoe domains and are mostly flanked by two cysteine clusters including two or four cysteine residue. Each of the six major TLR families is characterized by their constituent LRR motifs, their repeat numbers, and their patterns of cysteine clusters. The central parts of the TLR1 and TLR7 families and of TLR4 have more irregular or longer LRR motifs. These central parts are inferred to play a key role in the structure and/or function of their TLRs. Furthermore, the super-repeat in the TLR7 family suggests strongly that "bacterial" and "typical" LRRs evolved from a common precursor.

MeSH Terms
Amino Acid Motifs/genetics Amino Acid Sequence Animals Computational Biology Conserved Sequence/genetics Genetic Variation Humans Immunity, Innate/genetics Molecular Sequence Data Multigene Family/genetics Protein Structure, Secondary Protein Structure, Tertiary Sequence Alignment Toll-Like Receptors/genetics Vertebrates/genetics
Chemicals
Toll-Like Receptors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Matsushima Norio
School of Health Sciences, Sapporo Medical University, Hokkaido, Japan. [email protected]
Tanaka Takanori
Enkhbayar Purevjav
Mikami Tomoko
Taga Masae
Yamada Keiko
Kuroki Yoshio
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Article Info
Journal
BMC genomics
Abbr.
BMC Genomics
ISSN
1471-2164
DOI
10.1186/1471-2164-8-124
Email
[email protected]
Published
2007-05-21
Epub
2007-00-21
Pages
124
Language
English
Region
England
NLM ID
100965258
PMCID
PMC1899181
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-2164-8-124 PMC Full Text View journal details
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