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131.
The speed with which individuals can learn to identify and react appropriately to predation threats when transitioning to new life history stages and habitats will influence their survival. This study investigated the role of chemical alarm cues in both anti-predator responses and predator identification during a transitional period in a newly settled coral reef damselfish, Pomacentrus amboinensis. Individuals were tested for changes in seven behavioural traits in response to conspecific and heterospecific skin extracts. Additionally, we tested whether fish could learn to associate a previously novel chemical cue (i.e. simulated predator scent) with danger, after previously being exposed to a paired cue combining the conspecific skin extract with the novel scent. Fish exposed to conspecific skin extracts were found to significantly decreased their feeding rate whilst those exposed to heterospecific and control cues showed no change. Individuals were also able to associate a previously novel scent with danger after only a single previous exposure to the paired conspecific skin extract/novel scent cue. Our results indicate that chemical alarm cues play a large role in both threat detection and learned predator recognition during the early post-settlement period in coral reef fishes. 相似文献
132.
We extend recent modeling studies of proton hopping, used to describe the functioning of membrane channels and axon nerve conduction, to offer an explanation of the initiation of the nerve impulse at an effector? ligand encounter. This encounter is proposed to create a hydronium ion in the vicinity of the effector and ligand, which leads to a continuous flow of protons, called proton hopping, through water adjacent to this encounter. This proton hopping is proposed to be the message carried from the encounter to the axon of a particular nerve system associated with that particular effector? ligand system. 相似文献
133.
Pilar Martin-Marcos Jagpreet Nanda Rafael E. Luna Gerhard Wagner Jon R. Lorsch Alan G. Hinnebusch 《The Journal of biological chemistry》2013,288(38):27546-27562
Recognition of the translation initiation codon is thought to require dissociation of eIF1 from the 40 S ribosomal subunit, enabling irreversible GTP hydrolysis (Pi release) by the eIF2·GTP·Met-tRNAi ternary complex (TC), rearrangement of the 40 S subunit to a closed conformation incompatible with scanning, and stable binding of Met-tRNAi to the P site. The crystal structure of a Tetrahymena 40 S·eIF1 complex revealed several basic amino acids in eIF1 contacting 18 S rRNA, and we tested the prediction that their counterparts in yeast eIF1 are required to prevent premature eIF1 dissociation from scanning ribosomes at non-AUG triplets. Supporting this idea, substituting Lys-60 in helix α1, or either Lys-37 or Arg-33 in β-hairpin loop-1, impairs binding of yeast eIF1 to 40 S·eIF1A complexes in vitro, and it confers increased initiation at UUG codons (Sui− phenotype) or lethality, in a manner suppressed by overexpressing the mutant proteins or by an eIF1A mutation (17–21) known to impede eIF1 dissociation in vitro. The eIF1 Sui− mutations also derepress translation of GCN4 mRNA, indicating impaired ternary complex loading, and this Gcd− phenotype is likewise suppressed by eIF1 overexpression or the 17–21 mutation. These findings indicate that direct contacts of eIF1 with 18 S rRNA seen in the Tetrahymena 40 S·eIF1 complex are crucial in yeast to stabilize the open conformation of the 40 S subunit and are required for rapid TC loading and ribosomal scanning and to impede rearrangement to the closed complex at non-AUG codons. Finally, we implicate the unstructured N-terminal tail of eIF1 in blocking rearrangement to the closed conformation in the scanning preinitiation complex. 相似文献
134.
Johannes Schiebel Kanishk Kapilashrami Agnes Fekete Gopal R. Bommineni Christin M. Schaefer Martin J. Mueller Peter J. Tonge Caroline Kisker 《The Journal of biological chemistry》2013,288(47):34190-34204
The survival of Mycobacterium tuberculosis depends on mycolic acids, very long α-alkyl-β-hydroxy fatty acids comprising 60–90 carbon atoms. However, despite considerable efforts, little is known about how enzymes involved in mycolic acid biosynthesis recognize and bind their hydrophobic fatty acyl substrates. The condensing enzyme KasA is pivotal for the synthesis of very long (C38–42) fatty acids, the precursors of mycolic acids. To probe the mechanism of substrate and inhibitor recognition by KasA, we determined the structure of this protein in complex with a mycobacterial phospholipid and with several thiolactomycin derivatives that were designed as substrate analogs. Our structures provide consecutive snapshots along the reaction coordinate for the enzyme-catalyzed reaction and support an induced fit mechanism in which a wide cavity is established through the concerted opening of three gatekeeping residues and several α-helices. The stepwise characterization of the binding process provides mechanistic insights into the induced fit recognition in this system and serves as an excellent foundation for the development of high affinity KasA inhibitors. 相似文献
135.
Omri Faingold Avraham Ashkenazi Nathali Kaushansky Avraham Ben-Nun Yechiel Shai 《The Journal of biological chemistry》2013,288(46):32852-32860
An immunosuppressive motif was recently found within the HIV-1 gp41 fusion protein (termed immunosuppressive loop-associated determinant core motif (ISLAD CM)). Peptides containing the motif interact with the T-cell receptor (TCR) complex; however, the mechanism by which the motif exerts its immunosuppressive activity is yet to be determined. Recent studies showed that interactions between protein domains in the membrane milieu are not always sterically controlled. Therefore, we utilized the unique membrane leniency toward association between d- and l-stereoisomers to investigate the detailed mechanism by which ISLAD CM inhibits T-cell activation. We show that a d-enantiomer of ISLAD CM (termed ISLAD d-CM) inhibited the proliferation of murine myelin oligodendrocyte glycoprotein (MOG)-(35–55)-specific line T-cells to the same extent as the l-motif form. Moreover, the d- and l-forms preferentially bound spleen-derived T-cells over B-cells by 13-fold. Furthermore, both forms of ISLAD CM co-localized with the TCR on activated T-cells and interacted with the transmembrane domain of the TCR. FRET experiments revealed the importance of basic residues for the interaction between ISLAD CM forms and the TCR transmembrane domain. Ex vivo studies demonstrated that ISLAD d-CM administration inhibited the proliferation (72%) and proinflammatory cytokine secretion of pathogenic MOG(35–55)-specific T-cells. This study provides insights into the immunosuppressive mechanism of gp41 and demonstrates that chirality-independent interactions in the membrane can take place in diverse biological systems. Apart from HIV pathogenesis, the d-peptide reported herein may serve as a potential tool for treating T-cell-mediated pathologies. 相似文献
136.
Takayoshi Tagami Keitaro Yamashita Masayuki Okuyama Haruhide Mori Min Yao Atsuo Kimura 《The Journal of biological chemistry》2013,288(26):19296-19303
Sugar beet α-glucosidase (SBG), a member of glycoside hydrolase family 31, shows exceptional long-chain specificity, exhibiting higher kcat/Km values for longer malto-oligosaccharides. However, its amino acid sequence is similar to those of other short chain-specific α-glucosidases. To gain structural insights into the long-chain substrate recognition of SBG, a crystal structure complex with the pseudotetrasaccharide acarbose was determined at 1.7 Å resolution. The active site pocket of SBG is formed by a (β/α)8 barrel domain and a long loop (N-loop) bulging from the N-terminal domain similar to other related enzymes. Two residues (Phe-236 and Asn-237) in the N-loop are important for the long-chain specificity. Kinetic analysis of an Asn-237 mutant enzyme and a previous study of a Phe-236 mutant enzyme demonstrated that these residues create subsites +2 and +3. The structure also indicates that Phe-236 and Asn-237 guide the reducing end of long substrates to subdomain b2, which is an additional element inserted into the (β/α)8 barrel domain. Subdomain b2 of SBG includes Ser-497, which was identified as the residue at subsite +4 by site-directed mutagenesis. 相似文献
137.
Sosuke Yoshinaga Toru Sato Makoto Hirakane Kaori Esaki Takashi Hamaguchi Sachiko Haga-Yamanaka Mai Tsunoda Hiroko Kimoto Ichio Shimada Kazushige Touhara Hiroaki Terasawa 《The Journal of biological chemistry》2013,288(22):16064-16072
Exocrine gland-secreting peptide 1 (ESP1) is a sex pheromone that is released in male mouse tear fluids and enhances female sexual receptive behavior. ESP1 is selectively recognized by a specific class C G-protein-coupled receptor (GPCR), V2Rp5, among the hundreds of receptors expressed in vomeronasal sensory neurons (VSNs). The specific sensing mechanism of the mammalian peptide pheromone by the class C GPCR remains to be elucidated. Here we identified the minimal functional region needed to retain VSN-stimulating activity in ESP1 and determined its three-dimensional structure, which adopts a helical fold stabilized by an intramolecular disulfide bridge with extensive charged patches. We then identified the amino acids involved in the activation of VSNs by a structure-based mutational analysis, revealing that the highly charged surface is crucial for the ESP1 activity. We also demonstrated that ESP1 specifically bound to an extracellular region of V2Rp5 by an in vitro pulldown assay. Based on homology modeling of V2Rp5 using the structure of the metabotropic glutamate receptor, we constructed a docking model of the ESP1-V2Rp5 complex in which the binding interface exhibited good electrostatic complementarity. These experimental results, supported by the molecular docking simulations, reveal that charge-charge interactions determine the specificity of ESP1 binding to V2Rp5 in the large extracellular region characteristic of class C GPCRs. The present study provides insights into the structural basis for the narrowly tuned sensing of mammalian peptide pheromones by class C GPCRs. 相似文献
138.
Mary E. Heavner Gwenaelle Gueguen Roma Rajwani Pedro E. Pagan Chiyedza Small Shubha Govind 《Gene》2013
Analysis of natural host-parasite relationships reveals the evolutionary forces that shape the delicate and unique specificity characteristic of such interactions. The accessory long gland-reservoir complex of the wasp Leptopilina heterotoma (Figitidae) produces venom with virus-like particles. Upon delivery, venom components delay host larval development and completely block host immune responses. The host range of this Drosophila endoparasitoid notably includes the highly-studied model organism, Drosophila melanogaster. Categorization of 827 unigenes, using similarity as an indicator of putative homology, reveals that approximately 25% are novel or classified as hypothetical proteins. Most of the remaining unigenes are related to processes involved in signaling, cell cycle, and cell physiology including detoxification, protein biogenesis, and hormone production. Analysis of L. heterotoma's predicted venom gland proteins demonstrates conservation among endo- and ectoparasitoids within the Apocrita (e.g., this wasp and the jewel wasp Nasonia vitripennis) and stinging aculeates (e.g., the honey bee and ants). Enzyme and KEGG pathway profiling predicts that kinases, esterases, and hydrolases may contribute to venom activity in this unique wasp. To our knowledge, this investigation is among the first functional genomic studies for a natural parasitic wasp of Drosophila. Our findings will help explain how L. heterotoma shuts down its hosts' immunity and shed light on the molecular basis of a natural arms race between these insects. 相似文献
139.
Colloidal gold nanoparticles (AuNPs), with unique properties such as highly resonant particle plasmons, direct visualization of single nanoclusters by scattering of light, catalytic size enhancement by silver deposition, conductivity, and electrochemical properties, are very attractive materials for several applications in biotechnology. Furthermore, as excellent biological tags, AuNPs can be easily conjugated with biomolecules and retain the biochemical activity of the tagged biomolecules, making AuNPs ideal transducers for several biorecognition applications. The goal of this article is to review recent advances of using AuNPs as labels for signal amplification in biosensing applications. We focus on the signal amplification strategies of AuNPs in biosensing/biorecognition, more specifically, on the main optical and electrochemical detection methods that involve AuNP-based biosensing. Particular attention is given to recent advances and trends in sensing applications. 相似文献
140.