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41.
Watanabe K Chirgadze DY Lietha D de Jonge H Blundell TL Gherardi E 《Journal of molecular biology》2002,319(2):283-288
NK1 is a splice variant of the polypeptide growth factor HGF/SF that consists of the N terminal (N) and first kringle (K) domains and retains receptor binding and signalling. While NK1 behaves as a monomer in solution, two independent crystallographic structures have previously shown an identical, tightly packed dimer. Here we report a novel orthorhombic crystal form of NK1 at 2.5 A resolution in which four NK1 protomers are packed in two distinct dimers in the asymmetric unit. Although the basic architecture of the new NK1 dimers is similar to the two described earlier, the new crystal form demonstrates extensive hinge movement between the N and K domain that leads to re-orientation of the receptor-binding sites. The hinge bending is evidence of the paucity of strong interactions between domains within the protomer, in contrast to the extensive interactions between protomers in the dimer. These observations are consistent with domain swapping in the dimer, such that the interdomain interactions of the monomer are replaced by equivalent interprotomer interactions in the dimer and offer a route for protein engineering of NK1 variants which may act as receptor antagonists. 相似文献
42.
Relationship between SU subdomains that regulate the receptor-mediated transition from the native (fusion-inhibited) to the fusion-active conformation of the murine leukemia virus glycoprotein 下载免费PDF全文
Envelope glycoproteins (Env) of retroviruses are trimers of SU (surface) and TM (transmembrane) heterodimers and are expressed on virions in fusion-competent forms that are likely to be metastable. Activation of the viral receptor-binding domain (RBD) via its interaction with a cell surface receptor is thought to initiate a cascade of events that lead to refolding of the Env glycoprotein into its stable fusion-active conformation. While the fusion-active conformation of the TM subunit has been described in detail for several retroviruses, little is known about the fusion-competent structure of the retroviral glycoproteins or the molecular events that mediate the transition between the two conformations. By characterizing Env chimeras between the ecotropic and amphotropic murine leukemia virus (MLV) SUs as well as a set of point mutants, we show that alterations of the conformation of the SU glycoprotein strongly elevate Env fusogenicity by disrupting the stability of the Env complex. Compensatory mutations that restored both Env stability and fusion control were also identified, allowing definition of interactions within the Env complex that maintain the stability of the native Env complex. We show that, in the receptor-unbound form, structural interactions between the N terminus of the viral RBD (NTR domain), the proline-rich region (PRR), and the distal part of the C-terminal domain of the SU subunit maintain a conformation of the glycoprotein that is fusion inhibitory. Additionally, we identified mutations that disrupt this fusion-inhibitory conformation and allow fusion activation in the absence of viral receptors, provided that receptor-activated RBD fragments are added in trans during infection. Other mutations were identified that allow fusion activation in the absence of receptors for both the viral glycoprotein and the trans-acting RBD. Finally, we found mutations of the SU that bypass in cis the requirement for the NTR domain in fusion activation. All these different mutations call for a critical role of the PRR in mediating conformational changes of the Env glycoprotein during fusion activation. Our results suggest a model of MLV Env fusion activation in which unlocking of the fusion-inhibitory conformation is initiated by receptor binding of the viral RBD, which, upon disruption of the PRR, allows the NTR domain to promote further events in Env fusion activation. This involves a second type of interaction, in cis or in trans, between the receptor-activated RBD and a median segment of the freed C-terminal domain. 相似文献
43.
Absence of transitive and systemic pathways allows cell-specific and isoform-specific RNAi in Drosophila 总被引:3,自引:0,他引:3 下载免费PDF全文
Roignant JY Carré C Mugat B Szymczak D Lepesant JA Antoniewski C 《RNA (New York, N.Y.)》2003,9(3):299-308
RNA interference (RNAi) designates the multistep process by which double-stranded RNA induces the silencing of homologous endogenous genes. Some aspects of RNAi appear to be conserved throughout evolution, including the processing of trigger dsRNAs into small 21-23-bp siRNAs and their use to guide the degradation of complementary mRNAs. Two remarkable features of RNAi were uncovered in plants and Caenorhabditid elegans. First, RNA-dependent RNA polymerase activities allow the synthesis of siRNA complementary to sequences upstream of or downstream from the initial trigger region in the target mRNA, leading to a transitive RNAi with sequences that had not been initially targeted. Secondly, systemic RNAi may cause the targeting of gene silencing in one tissue to spread to other tissues. Using transgenes expressing dsRNA, we investigated whether transitive and systemic RNAi occur in DROSOPHILA: DsRNA-producing transgenes targeted RNAi to specific regions of alternative mRNA species of one gene without transitive effect directed to sequences downstream from or upstream of the initial trigger region. Moreover, specific expression of a dsRNA, using either cell-specific GAL4 drivers or random clonal activation of a GAL4 driver, mediated a cell-autonomous RNAi. Together, our results provide evidence that transitive and systemic aspects of RNAi are not conserved in Drosophila and demonstrate that dsRNA-producing transgenes allow powerful reverse genetic approaches to be conducted in this model organism, by knocking down gene functions at the resolution of a single-cell type and of a single isoform. 相似文献
44.
Pseudolernentoma, a new chondracanthid genus was proposed to accommodate Pseudolernentoma brasiliensis n. g., n. sp., parasitic on the pink cusk-eel Genypterus brasiliensis Regan, from off the coast of Rio de Janeiro, Brazil. The new genus can be differentiated from the other genera of the Chondracanthidae by the presence of an inflated head with lateral expansions and anteroventral bifurcate processes on the trunk. 相似文献
45.
46.
Martha P. Brown Dimitri Toptygin K. B. Lee Theresa Animashaun R. C. Hughes Y. C. Lee Ludwig Brand 《The protein journal》1998,17(2):149-159
The plant lectin Tetracarbidium conophorum agglutinin II binds to glycoproteins and glycopeptides in a structurally specific manner [Animashaun et al., (1994) Glycoconjugate J. 11, 299–303]. We have characterized the steady-state and time-resolved fluorescence of the tryptophan residues of this lectin. The fluorescence (λex = 295 nm, λem = 350 nm) decay is complex and can be described by four decay times with the following values: τ1 = 7.4nsec, α1 = 0.22; τ2 = 2.9 nsec, α2 = 0.25; τ3 = l.0 nsec, α3 = 0.34; τ4 = 0.2 nsec, α4 = 0.18. The addition of a biantennary glycopeptide $\begin{array}{*{20}c} {Gal\beta (1 \to 4)GlcNAc\beta (1 \to 2)Man\alpha (1 \to 6)\neg } \\ {Man\beta (1 \to 4)GlcNAC\beta (1 \to 4)GlcAc\beta (1 \to )\begin{array}{*{20}c} {Glu - Nh_2 } \\ | \\ {Asn} \\ | \\ {COOH} \\ \end{array} } \\ {Gal\beta (1 \to 4)GlcNAc\beta (1 \to 2)Man\alpha (1 \to 3)} \\ \end{array} $ to the lectin results in a quench and an 8 nm blue shift of the emission spectrum. The effect is saturable, and is described by an association constant of 1.8×105 M?1. The tryptophan fluorescence of Tetracarbidium conophorum agglutinin II may therefore be utilized to characterize thermodynamically the binding interactions between this lectin and complex glycoprotein. 相似文献
47.
48.
Martha P. Brown Dimitri Toptygin K. B. Lee Theresa Animashaun R. C. Hughes Y. C. Lee Ludwig Brand 《Journal of Protein Chemistry》1998,17(2):149-159
The plant lectin Tetracarbidium conophorum agglutinin II binds to glycoproteins and glycopeptides in a structurally specific manner [Animashaun et al., (1994) Glycoconjugate J.
11, 299–303]. We have characterized the steady-state and time-resolved fluorescence of the tryptophan residues of this lectin. The fluorescence (ex = 295 nm, em = 350 nm) decay is complex and can be described by four decay times with the following values: 1 = 7.4nsec, 1 = 0.22; 2 = 2.9 nsec, 2 = 0.25; 3 = l.0 nsec, 3 = 0.34; 4 = 0.2 nsec, 4 = 0.18. The addition of a biantennary glycopeptide
to the lectin results in a quench and an 8 nm blue shift of the emission spectrum. The effect is saturable, and is described by an association constant of 1.8×105 M–1. The tryptophan fluorescence of Tetracarbidium conophorum agglutinin II may therefore be utilized to characterize thermodynamically the binding interactions between this lectin and complex glycoprotein. 相似文献
49.
Michel Guipponi Federico A. Santoni Vincent Setola Corinne Gehrig Maud Rotharmel Macarena Cuenca Olivier Guillin Dimitris Dikeos Georgios Georgantopoulos George Papadimitriou Logos Curtis Alexandre Méary Franck Schürhoff Stéphane Jamain Dimitri Avramopoulos Marion Leboyer Dan Rujescu Ann Pulver Dominique Campion David P. Siderovski Stylianos E. Antonarakis 《PloS one》2015,10(10)
50.