Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors.
Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors.
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脊椎动物Toll样受体中富含亮氨酸重复序列（LRR）的比较序列分析。
DOI：
10.1186/1471-2164-8-124
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发表时间：
2007-05-21
期刊：
影响因子：
4.4
通讯作者：
Kuroki, Yoshio
中科院分区：
文献类型：
--
作者：
Matsushima, Norio;Tanaka, Takanori;Enkhbayar, Purevjav;Mikami, Tomoko;Taga, Masae;Yamada, Keiko;Kuroki, Yoshio
Toll样受体（TLR）在先天免疫中起着重要作用。TLR是膜糖蛋白，并且在胞外域中含有富含亮氨酸的重复序列（LRR）基序。TLR识别并响应于诸如脂多糖、肽聚糖、鞭毛蛋白和来自细菌或病毒的RNA的分子。TLR中的LRR结构域已被推断为负责分子识别。所有LRR都包括高度保守的区段LxxLxLxxNxL，其中“L”是Leu、Ile、瓦尔或Phe，“N”是Asn、Thr、Ser或Cys，“x”是任何氨基酸。LRR有七类，包括“典型”（“T”）和“细菌”（“S”）。所有已知的畴结构都采用弧形或马蹄形。脊椎动物TLR形成六个主要家族。LRR的重复数和它们在TLR中的“定相”随同种型和物种而不同;它们在各种数据库中不同地对齐。我们确定和TLRs中的LRR对齐这里描述的一种新方法。新方法利用已知的LRR结构来识别和比对TLR中的新LRR基序，并结合了多重序列比对和二级结构预测。分析了来自34种脊椎动物的TLR。LRR的重复数范围为16至28。在TLR中发现的LRR通常由LxxLxLxxNxLxxLxxxxF/LxxLxx（“T”）组成，有时短基序包括LxxLxLxxNxLxxLPx（x）LPxx（“S”）。TLR 7家族（TLR 7、TLR 8和TLR 9）包含27个LRR。LRR在N端部分具有约80个残基的STT超基序。超级重复序列由STTSTTSTT或_TTSTTSTT表示。TLR中的LRR形成一个或两个马蹄形结构域，并且大多侧接两个半胱氨酸簇，包括两个或四个半胱氨酸残基。六个主要TLR家族中的每一个的特征在于它们的组成LRR基序、它们的重复数和它们的半胱氨酸簇模式。TLR 1和TLR 7家族以及TLR 4的中心部分具有更不规则或更长的LRR基序。推测这些中心部分在其TLR的结构和/或功能中起关键作用。此外，TLR 7家族中的超级重复序列强烈表明“细菌”和“典型”LRR是从共同的前体进化而来的。
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.