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101.
Ott TR Pahuja A Nickolls SA Alleva DG Struthers RS 《The Journal of biological chemistry》2004,279(41):42383-42392
The binding pocket of family A GPCRs that bind small biogenic amines is well characterized. In this study we identify residues on CC chemokine receptor 7 (CCR-7) that are involved in agonist-mediated receptor activation but not in high affinity ligand binding. The mutations also affect the ability of the ligands to induce chemotaxis. Two of the residues, Lys3.33(137) and Gln5.42(227), are consistent with the binding pocket described for biogenic amines, while Lys3.26(130) and Asn7.32(305), are found at, or close to, the cell surface. Our observations are in agreement with findings from other peptide and chemokine receptors, which indicate that receptors that bind larger ligands contain contact sites closer to the cell surface in addition to the conventional transmembrane binding pocket. These findings also support the theory that chemokine receptors require different sets of interactions for high affinity ligand binding and receptor activation. 相似文献
102.
103.
David E. Ausband Michael S. Mitchell Sarah B. Bassing Andrea Morehouse Douglas W. Smith Daniel Stahler Jennifer Struthers 《Ethology : formerly Zeitschrift fur Tierpsychologie》2016,122(12):963-972
Variation in group composition and environment can affect helping behavior in cooperative breeders. Understanding of how group size, traits of individuals within groups, food abundance, and predation risk simultaneously influence helping behavior is limited. We evaluated pup‐guarding behavior in gray wolves (Canis lupus) to assess how differences in individuals, groups, and environment affect helping behavior. We used data from 92 GPS‐collared wolves in North America (2001–2012) to estimate individual pup‐guarding rates. Individuals in groups with low helper‐to‐pup ratios spent more time guarding young than those in groups with more helpers, an indication of load‐lightening. Female helpers guarded more than male helpers, but this relationship weakened as pups grew. Subset analyses including data on helper age and wolf and prey density showed such factors did not significantly influence pup‐guarding rates. We show that characteristics of individuals and groups have strong influences on pup‐guarding behavior in gray wolves, but environmental factors such as food abundance and predation risk from conspecifics were not influential. 相似文献
104.
We have used cysteine scanning mutagenesis and disulfide cross-linking in a split rhodopsin construct to investigate the secondary structure and tertiary contacts of the fifth (TM5) and sixth (TM6) transmembrane segments of rhodopsin. Using a simple increase in pH to promote disulfide bond formation, three cross-links between residues on the extracellular side of TM5 (at positions 198, 200, and 204) and TM6 (at position 276) have been identified and characterized. The helical pattern of cross-linking observed indicates that the fifth transmembrane helix extends through residue 200 but does not include residue 198. Rhodopsin mutants containing these disulfides demonstrate nativelike absorption spectra and light-dependent activation of transducin, suggesting that large movements on the extracellular side of TM5 with respect to TM6 are not required for receptor activation. 相似文献
105.
Atmospheric water vapor as driver of litter decomposition in Mediterranean shrubland and grassland during rainless seasons 总被引:2,自引:0,他引:2
INGA DIRKS YAEL NAVON DINA KANAS RITA DUMBUR JOSÉ M. GRÜNZWEIG 《Global Change Biology》2010,16(10):2799-2812
Litter production in many drought‐affected ecosystems coincides with the beginning of an extended season of no or limited rainfall. Because of lack of moisture litter decomposition during such periods has been largely ignored so far, despite potential importance for the overall decay process in such ecosystems. To determine drivers and extent of litter decay in rainless periods, a litterbag study was conducted in Mediterranean shrublands, dwarf shrublands and grasslands. Heterogeneous local and common straw litter was left to decompose in open and shaded patches of various field sites in two study regions. Fresh local litter lost 4–18% of its initial mass over about 4 months without rainfall, which amounted to 15–50% of total annual decomposition. Lab incubations and changes in chemical composition suggested that litter was degraded by microbial activity, enabled by absorption of water vapor from the atmosphere. High mean relative humidity of 85% was measured during 8–9 h of most nights, but the possibility of fog deposition or dew formation at the soil surface was excluded. Over 95% of the variation in mass loss and changes in litter nitrogen were explained by characteristics of water‐vapor uptake by litter. Photodegradation induced by the intense solar radiation was an additional mechanism of litter decomposition as indicated by lignin dynamics. Lignin loss from litter increased with exposure to ultraviolet radiation and with initial lignin concentration, together explaining 90%–97% of the variation in lignin mass change. Our results indicate that water vapor, solar radiation and litter quality controlled decomposition and changes in litter chemistry during rainless seasons. Many regions worldwide experience transient periods without rainfall, and more land area is expected to undergo reductions in rainfall as a consequence of climate change. Therefore, absorption of water vapor might play a role in decomposition and nutrient cycling in an increasing number of ecosystems. 相似文献
106.
Sullivan SK Brown MS Gao Y Loweth CJ Lio FM Crowe PD Struthers RS Betz SF 《Biochemistry》2006,45(51):15327-15337
Nonpeptide antagonists of the human gonadotropin-releasing hormone receptor (GnRH-R) have been the subject of considerable interest because of their potential as a new class of oral therapeutics for the treatment of sex hormone-dependent diseases and infertility. While many classes of competitive GnRH-R antagonists have been described, we present here the first characterization of an allosteric nonpeptide GnRH-R antagonist. Previously, 5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-ylmethyl)furan-2-carboxylic acid (2,4,6-trimethoxyphenyl)amide (here called Furan-1) had been demonstrated to be a potent GnRH-R antagonist both in vitro and in vivo. Using mutagenesis, the binding sites for Furan-1 and another potent nonpeptide antagonist (NBI-42902) have been mapped and are shown to be adjacent but nonoverlapping. Furan-1 is shown to affect the binding kinetics of radiolabeled peptide agonists as well as radiolabeled NBI-42902, and the kinetic data fit the allosteric ternary complex model. Furan-1 is considerably negatively cooperative with the nonpeptide antagonist and extremely negatively cooperative with the peptide agonist [125I-His5,d-Tyr6]GnRH so that it is nearly indistinguishable from an orthosteric competitive compound. Taken together, these data were used to develop a model of the nonpeptides bound to the GnRH-R binding site consistent with the current data. 相似文献
107.
Ott TR Lio FM Olshefski D Liu XJ Ling N Struthers RS 《Biochemical and biophysical research communications》2006,348(3):1089-1093
CC chemokine receptor 7 (CCR7), which regulates the trafficking of leucocytes to the secondary lymphoid organs, has two endogenous chemokine ligands: CCL19 and CCL21. Although both ligands possess similar affinities for the receptor and similar abilities to promote G protein activation and chemotaxis, they share only 25% sequence identity. Here, we show that substituting N-terminal six amino acids of CCL21 (SDGGAQ) for the corresponding N-terminal domain of CCL19 (GTNDAE) results in a chimeric chemokine that exhibits high affinity binding and G protein activation of CCR7. These data demonstrate that despite dissimilar sequences, the amino terminal hexapeptide of these two chemokines is capable of performing similar roles resulting in receptor activation. 相似文献
108.
Zhao L Guo Z Chen Y Hu T Wu D Zhu YF Rowbottom M Gross TD Tucci FC Struthers RS Xie Q Chen C 《Bioorganic & medicinal chemistry letters》2008,18(11):3344-3349
Optimization of a series of uracils bearing a 2-fluoro- or 2-chloro-3-methoxyphenyl group at the 5-position resulted in compounds such as 3d and 3f with subnanomolar binding affinity at the human GnRH receptor. While the 2-fluoro-3-methoxyphenyl compound 3a was characterized as a mixture of interchangeable atropisomers, the diastereoisomers of 2-chloro-3-methoxyphenyl analogs were separated. It was found that the aR-atropisomer was much more potent than the aS-isomer based on the X-ray crystal structure of 3h-II. 相似文献
109.
Regan CF Guo Z Chen Y Huang CQ Chen M Jiang W Rueter JK Coon T Chen C Saunders J Brown MS Betz SF Struthers RS Yang C Wen J Madan A Zhu YF 《Bioorganic & medicinal chemistry letters》2008,18(16):4503-4507
A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition. 相似文献
110.
P. J. Smith D. Steinke S. M. Mcveagh A. L. Stewart C. D. Struthers C. D. Roberts 《Journal of fish biology》2008,73(5):1170-1182
Two regions of mtDNA, cytochrome b and cytochrome c oxidase subunit 1, were sequenced in nine species of Bathyraja from the Southern Ocean and New Zealand. Based on sequence divergence, the species that has been referred to as Bathyraja eatonii from the Antarctic continental shelf and slope is a species distinct from B. eatonii from the Kerguelen Plateau (the type locality) and is a new and undescribed species Bathyraja sp. (cf. eatonii). There was no sequence divergence among samples of Bathyraja sp. (dwarf) from the Ross Sea and the South Atlantic. However, for both Bathyraja sp. (cf. eatonii) and Bathyraja maccaini in the Ross Sea and the South Atlantic Ocean, the DNA sequence divergences indicate differentiation among ocean basins and within Bathyraja sp. (cf. eatonii) divergences are similar to those among recognized species of Bathyraja in the North Pacific Ocean. 相似文献