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1.
2.
NMR studies of the backbone protons and secondary structure of pentapeptide and heptapeptide substrates bound to bovine heart protein kinase 总被引:2,自引:0,他引:2
The conformations of enzyme-bound pentapeptide (Arg-Arg-Ala-Ser-Leu) and heptapeptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly) substrates of protein kinase have been studied by NMR in quaternary complexes of the type (Formula: see text). Paramagnetic effects of Mn2+ bound at the inhibitory site of the catalytic subunit on the longitudinal relaxation rates of backbone Ca protons, as well as on side-chain protons of the bound pentapeptide and heptapeptide substrates, have been used to determine Mn2+ to proton distances which range from 8.2 to 12.4 A. A combination of the paramagnetic probe-T1 method with the Redfield 2-1-4-1-2 pulse sequence for suppression of the water signal has been used to measure distances from Mn2+ to all of the backbone amide (NH) protons of the bound pentapeptide and heptapeptide substrates, which range from 6.8 to 11.1 A. Paramagnetic effects on the transverse relaxation rates yield rate constants for peptide exchange, indicating that the complexes studied by NMR dissociate rapidly enough to participate in catalysis. Model-building studies based on the Mn2+-proton distances, as well as on previously determined distances from Cr3+-AMPPCP to side-chain protons [Granot, J., Mildvan, A.S., Bramson, H. N., & Kaiser, E. T. (1981) Biochemistry 20, 602], rule out alpha-helical, beta-sheet, beta-bulge, and all possible beta-turn conformations within the bound pentapeptide and heptapeptide substrates. The distances are fit only by extended coil conformations for the bound peptide substrates with a minor difference between the pentapeptides and heptapeptides in the phi torsional angle at Arg3C alpha and in psi at Arg2C alpha. An extended coil conformation, which minimizes the number of interactions within the substrate, would facilitate enzyme-substrate interaction and could thereby contribute to the specificity of protein kinase. 相似文献
3.
B L Doughty E A Ottesen T E Nash S M Phillips 《Journal of immunology (Baltimore, Md. : 1950)》1984,133(2):993-997
An in vitro model of granuloma formation was used to study the cellular immune responses of Schistosoma mansoni-infected patients. The purposes of this study were to determine the relationship of granulomatous hypersensitivity to S. mansoni eggs in recent, well-defined infections and long-term chronic infections, and to determine the role of T cell subsets (OKT3, 4, and 8) defined by monoclonal antibodies in granulomatous hypersensitivity. Peripheral blood mononuclear cells obtained from patients with recent S. mansoni infections demonstrated increased granulomatous hypersensitivity responses in vitro when compared to peripheral blood mononuclear cells obtained from patients infected for 5 yr or more. The selective removal of infected for 5 yr or more. The selective removal of OKT3+ or OKT4+ cells reduced the ability of peripheral blood mononuclear cells to form granulomas in vitro. Positive selection for OKT4+ T cells produced optimal granulomatous hypersensitivity when compared to that produced by the unfractionated peripheral blood mononuclear cell population. OKT8+ cells demonstrated no ability to form granulomas in vitro. Selective removal of OKT8+ T cells produced variable results in the ability of the remaining peripheral blood mononuclear cells to form granulomas in vitro. These studies demonstrate the feasibility of investigating granulomatous hypersensitivity and immunoregulatory mechanisms operative in S. mansoni-infected patients by using in vitro technology. 相似文献
4.
Simona Picardi Briana Abrahms Emily Gelzer Thomas A. Morrison Tana Verzuh Jerod A. Merkle 《Ecology letters》2023,26(1):157-169
Site fidelity—the tendency to return to previously visited locations—is widespread across taxa. Returns may be driven by several mechanisms, including memory, habitat selection, or chance; however, pattern-based definitions group different generating mechanisms under the same label of ‘site fidelity’, often assuming memory as the main driver. We propose an operational definition of site fidelity as patterns of return that deviate from a null expectation derived from a memory-free movement model. First, using agent-based simulations, we show that without memory, intrinsic movement characteristics and extrinsic landscape characteristics are key determinants of return patterns and that even random movements may generate substantial probabilities of return. Second, we illustrate how to implement our framework empirically to establish ecologically meaningful, system-specific null expectations for site fidelity. Our approach provides a conceptual and operational framework to test hypotheses on site fidelity across systems and scales. 相似文献
5.
Niraj Shrestha Pallavi Chaturvedi Xiaoyun Zhu Michael J. Dee Varghese George Christopher Janney Jack O. Egan Bai Liu Mark Foster Lynne Marsala Pamela Wong Celia C. Cubitt Jennifer A. Foltz Jennifer Tran Timothy Schappe Karin Hsiao Gilles M. Leclerc Lijing You Christian Echeverri Catherine Spanoudis Ana Carvalho Leah Kanakaraj Crystal Gilkes Nicole Encalada Lin Kong Meng Wang Byron Fang Zheng Wang Jin-an Jiao Gabriela J. Muniz Emily K. Jeng Nicole Valdivieso Liying Li Richard Deth Melissa M. Berrien-Elliott Todd A. Fehniger Peter R. Rhode Hing C. Wong 《Aging cell》2023,22(5):e13806
6.
Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell-signaling events upon binding to active G-protein coupled receptors (GPCR) and trigger endocytosis of active GPCRs. While many of the functional sites on arrestins have been characterized, the question of how these sites interact is unanswered. We used anisotropic network modeling (ANM) together with our covariance compliment techniques to survey all the available structures of the nonvisual arrestins to map how structural changes and protein-binding affect their structural dynamics. We found that activation and clathrin binding have a marked effect on arrestin dynamics, and that these dynamics changes are localized to a small number of distant functional sites. These sites include α-helix 1, the lariat loop, nuclear localization domain, and the C-domain β-sheets on the C-loop side. Our techniques suggest that clathrin binding and/or GPCR activation of arrestin perturb the dynamics of these sites independent of structural changes. 相似文献
7.
Emily H. Waddell Daniel S. Chapman Jane K. Hill Mark Hughes Azlin Bin Sailim Joseph Tangah Lindsay F. Banin 《Biotropica》2023,55(4):767-778
Intact tropical forests are generally considered to be resistant to invasions by exotic species, although the shrub Clidemia hirta (Melastomataceae) is highly invasive in tropical forests outside its native range. Release from natural enemies (e.g., herbivores and pathogens) contributes to C. hirta invasion success where native melastomes are absent, and here we examine the role of enemies when C. hirta co-occurs with native Melastomataceae species and associated herbivores and pathogens. We study 21 forest sites within agricultural landscapes in Sabah, Malaysian Borneo, recording herbivory rates in C. hirta and related native Melastoma spp. plants along two 100-m transects per site that varied in canopy cover. Overall, we found evidence of enemy release; C. hirta had significantly lower herbivory (median occurrence of herbivory per plant = 79% of leaves per plant; median intensity of herbivory per leaf = 6% of leaf area) than native melastomes (93% and 20%, respectively). Herbivory on C. hirta increased when closer to native Melastoma plants with high herbivory damage, and in more shaded locations, and was associated with fewer reproductive organs on C. hirta. This suggests host-sharing by specialist Melastomataceae herbivores is occurring and may explain why invasion success of C. hirta is lower on Borneo than at locations without related native species present. Thus, natural enemy populations may provide a “biological control service” to suppress invasions of exotic species (i.e., biotic resistance). However, lower herbivory pressures in more open canopy locations may make highly degraded forests within these landscapes more susceptible to invasion. 相似文献
8.
Paul L. Doughty 《American anthropologist》2003,105(2):401-402
Culture and Rights: Anthropological Perspectives. Jane K. Cowan. Marie-Bénédicte Dembour. and Richard A. Wilson. eds. Cambridge: Cambridge University Press, 2001. 258 pp. 相似文献
9.
Borislav S. Stanchev James Doughty Charles P. Scutt Hugh Dickinson Ronald R.D. Croy 《The Plant journal : for cell and molecular biology》1996,10(2):303-313
The pollen coatings of both Brassica oleracea and Brassica napus contain a small family of basic 6–8 kDa proteins which are released on to the stigmatic surface on pollination. Following partial amino-acid sequencing of one of these pollen coat proteins (PCPs), PCR primers were constructed to isolate the PCP sequence from anther mRNA using RT-PCR. A cDNA was obtained which, in Northern hybridization experiments, revealed a characteristic pattern of expression during late stages of anther development. Interestingly, in situ hybridization revealed expression of this sequence to be confined to the cytoplasm of the trinucleate pollen grains: no signal was detected in the tapetum. Southern hybridization experiments have shown the gene ( PCP1 ) to be a member of a large family of between 30 and 40 PCP genes in the genome of Brassica oleracea , Surprisingly, RFLP experiments showed reduced copy number (one to two copies) in some of the F2 segregants, perhaps resulting from the clustering of PCP sequences. PCP1 contains a single intron and encodes a small, basic peptide 83 amino acids in length featuring a hydrophobic signal peptide sequence separated from the more hydrophilic, cysteine-rich mature protein. The central part and C-terminal region of the peptide contain a characteristic and invariant pattern of eight cysteines which show clear homology with a number of other anther-specific genes; the remainder of the sequence shows little similarity to other sequences on the data bases. The product of PCP1 is a member of a large family of similar proteins, some of which have been demonstrated to bind specifically to S-locus glycoproteins, but does not appear to be genetically linked to the S-locus . 相似文献
10.
David L. Cheo Lisiane B. Meira Robert E. Hammer Dennis K. Burns Ana T.B. Doughty Errol C. Friedberg 《Current biology : CB》1996,6(12)
The significance of DNA repair to human health has been well documented by studies on xeroderma pigmentosum (XP) patients, who suffer a dramatically increased risk of cancer in sun-exposed areas of their skin [1] and [2]. This autosomal recessive disorder has been directly associated with a defect in nucleotide excision–repair (NER) [1] and [2]. Like human XP individuals, mice carrying homozygous mutations in XP genes manifest a predisposition to skin carcinogenesis following exposure to ultraviolet (UV) radiation [3], [4] and [5]. Recent studies have suggested that, in addition to roles in apoptosis [6] and cell-cycle checkpoint control [7] in response to DNA damage, p53 protein may modulate NER [8]. Mutations in the p53 gene have been observed in 50% of all human tumors [9] and have been implicated in both the early [10] and late [11] stages of skin cancer. To examine the consequences of a combined deficiency of the XPC and the p53 proteins in mice, we generated double-mutant animals. We document a spectrum of neural tube defects in XPC p53 mutant embryos. Additionally, we show that, following exposure to UV-B radiation, XPC p53 mutant mice have more severe solar keratosis and suffer accelerated skin cancer compared with XPC mutant mice that are wild-type with respect to p53. 相似文献