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61.
L.M. Sampaleanu M. Ayers S. Tammam S.K. Burley L.L. Burrows P.L. Howell 《Journal of molecular biology》2009,394(1):143-159
Type IV pili (T4P) are bacterial virulence factors responsible for attachment to surfaces and for twitching motility, a motion that involves a succession of pilus extension and retraction cycles. In the opportunistic pathogen Pseudomonas aeruginosa, the PilM/N/O/P proteins are essential for T4P biogenesis, and genetic and biochemical analyses strongly suggest that they form an inner-membrane complex. Here, we show through co-expression and biochemical analysis that the periplasmic domains of PilN and PilO interact to form a heterodimer. The structure of residues 69-201 of the periplasmic domain of PilO was determined to 2.2 Å resolution and reveals the presence of a homodimer in the asymmetric unit. Each monomer consists of two N-terminal coiled coils and a C-terminal ferredoxin-like domain. This structure was used to generate homology models of PilN and the PilN/O heterodimer. Our structural analysis suggests that in vivo PilN/O heterodimerization would require changes in the orientation of the first N-terminal coiled coil, which leads to two alternative models for the role of the transmembrane domains in the PilN/O interaction. Analysis of PilN/O orthologues in the type II secretion system EpsL/M revealed significant similarities in their secondary structures and the tertiary structures of PilO and EpsM, although the way these proteins interact to form inner-membrane complexes appears to be different in T4P and type II secretion. Our analysis suggests that PilN interacts directly, via its N-terminal tail, with the cytoplasmic protein PilM. This work shows a direct interaction between the periplasmic domains of PilN and PilO, with PilO playing a key role in the proper folding of PilN. Our results suggest that PilN/O heterodimers form the foundation of the inner-membrane PilM/N/O/P complex, which is critical for the assembly of a functional T4P complex. 相似文献
62.
63.
The objective was to determine whether the inhalation of large quantities of feedyard dust predisposed the animals to pulmonary bacterial proliferation. Two control groups, C1 and C2, did not receive dust treatments, and two principal groups (P1 and P2) received a total of 14 dust treatments each. The C1 and P1 groups of goats each received a transthoracic challenge of live Mannheimia haemolytica (4 x 10(6) colony forming units, CFU) The C2 and P2 groups of goats each received a transthoracic challenge of live Pasteurella multocida (1.0 x 10(6) CFU/goat). The results showed that dusted animals had fever when compared with non-dusted controls. In addition, dusted animals demonstrated a leukocytosis with neutrophilia after the first dust treatment that was not sustainable. Finally, dusted animals demonstrated pulmonary clearance of two potential bacterial pathogens that was not significantly different from that shown by control (not dusted) animals. 相似文献
64.
Nucleotide variation in the triosephosphate isomerase (Tpi) locus of Drosophila melanogaster and Drosophila simulans 总被引:3,自引:0,他引:3
Hasson E; Wang IN; Zeng LW; Kreitman M; Eanes WF 《Molecular biology and evolution》1998,15(6):756-769
DNA sequence variation in a 1.1-kb region including the coding portion of
the Tpi locus was examined in 25 homozygous third-chromosome lines of
Drosophila melanogaster, nine lines of Drosophila simulans, and one line of
Drosophila yakuba. Our data show that the widespread allozyme polymorphism
observed in cosmopolitan D. melanogaster is due to a glutamic acid
substitution occurring in a phylogenetically conserved lysine that has been
identified as part of the "hinged-lid" active site of the enzyme. This
observation suggests that the replacement polymorphism may have important
functional consequences. One replacement polymorphism was also observed in
D. simulans, although its functional relevance is more difficult to assess,
since it affects a site that is not strongly conserved. This amino acid
change in D. simulans is associated with a single lineage possessing seven
unique silent substitutions, which may be indicative of balancing selection
or population subdivision. The absence of fixed amino acid differences
between D. melanogaster and D. simulans and only a single difference with
D. yakuba suggests that triose phosphate isomerase is under strong
functional constraint. Silent variation is slightly higher for D.
melanogaster than for D. simulans. Finally, we outline the general lack of
evidence for old balanced polymorphisms at allozyme loci in D.
melanogaster.
相似文献
65.
Host-Pathogen Interactions: XII. Response of Suspension-cultured Soybean Cells to the Elicitor Isolated from Phytophthora megasperma var. sojae, a Fungal Pathogen of Soybeans 下载免费PDF全文
The glucan elicitor isolated from the mycelial walls of Phytophthora megasperma var. sojae, the fungus which causes stem and root rot in soybeans, stimulates the activity of phenylalanine ammonia-lyase and the accumulation of glyceollin in suspension-cultured soybean cells. Nigeran, a commercially available fungal wall glucan, was the only other compound tested which has any activity in this system. Glyceollin is a phenylpropanoid-derived phytoalexin which is toxic to P. megasperma var. sojae. Evidence is presented to support the hypothesis that the action of elicitors in stimulating phytoalexin synthesis is not species or variety specific but, rather, is part of a general defensive response of plants. 相似文献
66.
Early glial responses in murine models of multiple sclerosis 总被引:4,自引:0,他引:4
Ayers MM Hazelwood LJ Catmull DV Wang D McKormack Q Bernard CC Orian JM 《Neurochemistry international》2004,45(2-3):409-419
Investigations of functional interactions among axons and glia over the last decade have revealed the extent and complexity of glial-neuronal and glial-glial communication during development, adult function and recovery from injury. These data have profound implications for the understanding of central nervous system (CNS) disorders, which until recently, have been classified as either neuronal or glial diseases. Re-evaluation of the pathological processes in a number of conditions has clearly shown involvement of both neurons and glia in early pathology. In multiple sclerosis (MS), the myelin sheath has traditionally been regarded as the primary target. However, recent evidence has clearly demonstrated axonal damage in new lesions. We have addressed the question of the role of axonal pathology in early MS by using well-characterized murine models for the relapsing-remitting (RR) or the primary progressive (PP) forms of the disease. We performed a histopathological survey of the CNS, following induction of the disease, to determine the timing of appearance, as well as the development of lesions. Then we analysed the relationship between inflammation, demyelination and axonal damage together with responses from astrocytes and microglia in each model from the earliest evidence of inflammation. We found that axonal damage begins well ahead of the appearance of motor symptoms. Pathology appears to be more closely related to the degree of inflammation than to demyelination. We also show that early astrocyte responses and the degree of axonal loss are markedly different in the two models and relate to the severity of pathology. These data support the now widely accepted hypothesis that axonal damage begins early in the disease process, but also suggest modulation of axonal loss and disease progression by the astrocytic response. 相似文献
67.
Subtype-selective nicotinic receptor antagonists: potential as tobacco use cessation agents 总被引:3,自引:0,他引:3
Dwoskin LP Sumithran SP Zhu J Deaciuc AG Ayers JT Crooks PA 《Bioorganic & medicinal chemistry letters》2004,14(8):1863-1867
N-n-Alkylpicolinium and N,N'-alkyl-bis-picolinium analogues were assessed in nicotinic receptor (nAChR) assays. The most potent and subtype-selective analogue, N,N'-dodecyl-bis-picolinium bromide (bPiDDB), inhibited nAChRs mediating nicotine-evoked [(3)H]dopamine release (IC(50)=5 nM; I(max) of 60%), and did not interact with alpha4beta2* or alpha7* nAChRs. bPiDDB represents the current lead compound for development as a tobacco use cessation agent. 相似文献
68.
Crooks PA Ayers JT Xu R Sumithran SP Grinevich VP Wilkins LH Deaciuc AG Allen DD Dwoskin LP 《Bioorganic & medicinal chemistry letters》2004,14(8):1869-1874
N-n-Alkylation of nicotine converts it from an agonist into an antagonist at neuronal nicotinic acetylcholine receptor subtypes mediating nicotine-evoked dopamine release. Conformationally restricted analogues exhibit both high affinity and selectivity at this site, and are able to access the brain due to their ability to act as substrates for the blood-brain barrier choline transporter. 相似文献
69.
Phylogenetic studies are often hampered by the independent evolution of characters that may potentially obscure relationships. The adaptive significance of the nectar spur and its evolution within the Mexican lobeliads (Campanulaceae) is considered here. The taxonomic delimitations of Heterotoma from the Mexican species within the genera Lobelia and Calcaratolobelia were tested. Independent molecular data were gathered to determine whether the Mexican spurred lobeliads should be treated as distinct genera. The internal transcribed spacer (ITS) region from 18-26S nuclear rDNA and chloroplast DNA from the 3' trnK intron were sequenced from 14 representative species. Our data suggest that Heterotoma, as originally conceived, is a good evolutionary unit within Lobelia and that the presence of a nectar spur is an important morphological character that can be used in defining phylogenetic position. This study also suggests that morphological changes associated with hummingbird pollination have evolved more than once in the Mexican lobeliads, from small blue-flowered, insect-pollinated relatives. 相似文献
70.