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

<p>Abstract</p> <p>Background</p> <p>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" ("<b><it>T</it></b>") and "bacterial" ("<b><it>S</it></b>"). 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.</p> <p>Results</p> <p>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 ("<b><it>T</it></b>") and sometimes short motifs including LxxLxLxxNxLxxLPx(x)LPxx ("<b>S</b>"). The <it>TLR7 </it>family (TLR7, TLR8, and TLR9) contain 27 LRRs. The LRRs at the N-terminal part have a super-motif of <b><it>STT </it></b>with about 80 residues. The super-repeat is represented by <b><it>STTSTTSTT </it></b>or <b><it>_TTSTTSTT</it></b>. The LRRs in TLRs form one or two horseshoe domains and are mostly flanked by two cysteine clusters including two or four cysteine residue.</p> <p>Conclusion</p> <p>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 <it>TLR1 </it>and <it>TLR7 </it>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 <it>TLR7 </it>family suggests strongly that "bacterial" and "typical" LRRs evolved from a common precursor.</p

Rhabdomyolysis secondary to hypervirulent Klebsiella pneumoniae infection: A case report

Abstract Hypervirulent Klebsiella pneumoniae (hvKP) is recognized as a lifethreatening community‐acquired infection associated with pyogenic liver abscess. However, rhabdomyolysis secondary to hvKP infection is rare. To the best of our knowledge, we report the first case of rhabdomyolysis due to hvKP infection in a patient who survived septic shock syndrome

Melanoma growth and tumorigenicity in models of microgravity

Spaceflight involves numerous biological stressors that could affect long-term cancer incidence and tumor behavior. Ground-based models of microgravity can be used to investigate in vitro and in vivo tumor growth as a preparation for later work in space. The incidence of tumor growth and carcinogenesis in microgravity is as yet unknown. Hence, we investigated the effects of modeled microgravity on tumor growth and tumorigenicity using ground-based in vitro and in vivo models