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Gifford RJ 《Trends in genetics : TIG》2012,28(2):89-100
Lentiviruses are a distinctive genus of retroviruses that cause chronic, persistent infections in mammals, including humans. The emergence of pandemic HIV type-1 (HIV-1) infection during the late 20th century shaped a view of lentiviruses as 'modern' viruses. However, recent research has revealed an entirely different perspective, elucidating aspects of an evolutionary relationship with mammals that extends across many millions of years. Such deep evolutionary history is likely to be typical of many host-virus systems, fundamentally underpinning their interactions in the present day. For this reason, establishing the deep history of virus and host interaction is key to developing a fully informed approach to tackling viral diseases. Here, I use the example of lentiviruses to illustrate how paleovirological, geographic and genetic calibrations allow observations of virus and host interaction across a wide range of temporal and spatial scales to be integrated into a coherent ecological and evolutionary framework. 相似文献
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The L-selectin glycoprotein receptor mediates the initial steps of leukocyte migration into secondary lymphoid organs and sites of inflammation. Following cell activation through the engagement of G-protein-coupled receptors or immunoreceptors, the extracellular domains of L-selectin are rapidly shed, a process negatively controlled via the binding of the ubiquitous eukaryotic calcium-binding protein calmodulin to the cytoplasmic tail of L-selectin. Here we present the solution structure of calcium-calmodulin bound to a peptide encompassing the cytoplasmic tail and part of the transmembrane domain of L-selectin. The structure and accompanying biophysical study highlight the importance of both calcium and the transmembrane segment of L-selectin in the interaction between these two proteins, suggesting that by binding this region, calmodulin regulates in an "inside-out" fashion the ectodomain shedding of the receptor. Our structure provides the first molecular insight into the emerging new role for calmodulin as a transmembrane signaling partner. 相似文献
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Calcium- and integrin-binding protein 1 (CIB1) is a ubiquitous, multifunctional regulatory protein consisting of four helix-loop-helix EF-hand motifs. Neither EF-I nor EF-II binds divalent metal ions; however, EF-III is a mixed Mg2+/Ca2+-binding site, and EF-IV is a higher-affinity Ca2+-specific site. Through the generation of several CIB1 mutant proteins, we have investigated the importance of the last (-Z) metal-coordinating position of EF-III (D127) and EF-IV (E172) with respect to the binding of CIB1 to Mg2+, Ca2+, and its biological target, the cytoplasmic domain of the platelet alphaIIb integrin. A D127N mutant had reduced Mg2+ and Ca2+ affinity at EF-III but retained affinity for the alphaIIb domain. A D127E mutant had increased Mg2+ and Ca2+ affinity at EF-III, but unexpectedly, the affinity for the alphaIIb domain was too low for binding to be observed. E172Q and E172D mutants showed no and weak Mg2+ binding at EF-IV, respectively, and each mutant had reduced Ca2+ affinity at EF-IV and showed moderate metal-dependent differences in affinity for the alphaIIb domain. Finally, a D127Q mutant bound Mg2+ and Ca2+ in a manner similar to that of D127N, but like that of D127E, the affinity for the alphaIIb domain was reduced below the detection limit. These data, combined with a NMR-based structural comparison of the Mg2+- and Ca2+-loaded CIB1-alphaIIb peptide complexes, suggest that the D127E and D127Q mutations have a disruptive effect on alphaIIb binding since they expand the metal-binding loop and change the alpha-helix positions in EF-III. Conversely, upon replacement of the ancestral Glu with Asp at the -Z position of EF-III, CIB1 gained affinity for alphaIIb, and the Ca2+ affinity of CIB1 shifted into a range where the protein is able to act as an intracellular Ca2+ sensor. 相似文献
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A “double-blepharoplast” originates de novo in the spermatogenous cell of Ginkgo biloba L. Initially, the double-blepharoplast consists of two opposing hemispherical bodies comprised of densely staining material. The two blepharoplasts seemingly are pushed apart by the formation of densely packed fibrils which are oriented perpendicular to the distal, rounded edges of the two future blepharoplasts. As the latter move apart, each one develops lightly staining channels which are often organized in a hub and spoke configuration (procentrioles). Microtubules extend from the blepharoplasts as the latter move to their final position in the cell, and centrioles (probasal bodies) become organized at the periphery of each blepharoplast. Two large “osmiophilic globules,” conspicuous entities close to the nucleus of the mature spermatogenous cell, arise de novo. A fibrillogranular body in the cytoplasm, always closely associated with the nucleus, also arises de novo. 相似文献
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