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61.
Veshnyakova A Piontek J Protze J Waziri N Heise I Krause G 《The Journal of biological chemistry》2012,287(3):1698-1708
Claudins (Cld) are essential constituents of tight junctions. Domain I of Clostridium perfringens enterotoxin (cCPE) binds to the second extracellular loop (ECL2) of a subset of claudins, e.g. Cld3/4 and influences tight junction formation. We aimed to identify interacting interfaces and to alter claudin specificity of cCPE. Mutagenesis, binding assays, and molecular modeling were performed. Mutation-guided ECL2 docking of Cld3/4 onto the crystal structure of cCPE revealed a common orientation of the proposed ECL2 helix-turn-helix motif in the binding cavity of cCPE: residues Leu(150)/Leu(151) of Cld3/4 bind similarly to a hydrophobic pit formed by Tyr(306), Tyr(310), and Tyr(312) of cCPE, and Pro(152)/Ala(153) of Cld3/4 is proposed to bind to a second pit close to Leu(223), Leu(254), and Leu(315). However, sequence variation in ECL2 of these claudins is likely responsible for slightly different conformation in the turn region, which is in line with different cCPE interaction modes of Cld3 and Cld4. Substitutions of other so far not characterized cCPE residues lining the pocket revealed two spatially separated groups of residues (Leu(223), Asp(225), and Arg(227) and Leu(254), lle(258), and Asp(284)), which are involved in binding to Cld3 and Cld4, albeit differently. Involvement of Asn(148) of Cld3 in cCPE binding was confirmed, whereas no evidence for involvement of Lys(156) or Arg(157) was found. We show structure-based alteration of cCPE generating claudin binders, which interact subtype-specific preferentially either with Cld3 or with Cld4. The obtained mutants and mechanistic insights will advance the design of cCPE-based modulators to target specific claudin subtypes related either to paracellular barriers that impede drug delivery or to tumors. 相似文献
62.
Jayne E Rattray Marc Strous Huub JM Op den Camp Stefan Schouten Mike SM Jetten Jaap S Sinninghe Damsté 《Biology direct》2009,4(1):8-16
Background
The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway. 相似文献63.
64.
Background
Analysis of heart rate variation (HRV) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system (ANS). HRV analysis is based on the concept that fast fluctuations may specifically reflect changes of sympathetic and vagal activity. It shows that the structure generating the signal is not simply linear, but also involves nonlinear contributions. These signals are essentially non-stationary; may contain indicators of current disease, or even warnings about impending diseases. The indicators may be present at all times or may occur at random in the time scale. However, to study and pinpoint abnormalities in voluminous data collected over several hours is strenuous and time consuming. 相似文献65.
Evolution of transposable elements: an IS10 insertion increases fitness in Escherichia coli 总被引:3,自引:0,他引:3
Strains of Escherichia coli carrying Tn10, a transposon consisting of two
IS10 insertion sequences flanking a segment encoding for a
tetracycline-resistance determinant, gain a competitive advantage in
chemostat cultures. All Tn10-bearing strains that increase in frequency
during competition have a new IS10 insertion that is found in the same
location in the genome of those strains. We mapped, by a gradient of
transmission, the position of the new IS10 insertion. We examined 11
isolates whose IS10 insertion was deleted by recombinational crossing-
over, and in all cases the competitive fitness of the isolates was
decreased. These results show that the IS10-generated insertion increases
fitness in chemostat cultures. We named the insertion fit::IS10 and suggest
that transposable elements may speed the rate of evolution by promoting
nonhomologous recombination between preexisting variations within a genome
and thereby generating adaptive variation.
相似文献
66.
Members of the ZFY and ZNF6 gene families have been cloned from species
representing different taxa and different modes of sex determination.
Comparisons of these genes show the ZFY-like and ZNF6 sequences to be
strongly conserved across marsupials, birds, and lepidosaurians. Sequence
analyzed by neighbor-joining indicated that both gene families are
monophyletic with a high bootstrap value. Pairing of sequences from males
and females of nonmammalian species showed there to be no significant
difference between male and female sequences from a single species,
consistent with autosomal locations. The molecular distances between murine
Zfy-1, Zfy-2, and other ZFY-like sequences suggested that Zfy genes have
undergone a period of rapid evolutionary change not seen in human ZFY.
相似文献
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