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Tufan G?kirmak Joseph P. Campanale Lauren E. Shipp Gary W. Moy Houchao Tao Amro Hamdoun 《The Journal of biological chemistry》2012,287(52):43876-43883
In this study, we cloned, expressed and functionally characterized Stronglycentrotus purpuratus (Sp) ATP-binding cassette (ABC) transporters. This screen identified three multidrug resistance (MDR) transporters with functional homology to the major types of MDR transporters found in humans. When overexpressed in embryos, the apical transporters Sp-ABCB1a, ABCB4a, and ABCG2a can account for as much as 87% of the observed efflux activity, providing a robust assay for their substrate selectivity. Using this assay, we found that sea urchin MDR transporters export canonical MDR susbtrates such as calcein-AM, bodipy-verapamil, bodipy-vinblastine, and mitoxantrone. In addition, we characterized the impact of nonconservative substitutions in the primary sequences of drug binding domains of sea urchin versus murine ABCB1 by mutation of Sp-ABCB1a and treatment of embryos with stereoisomeric cyclic peptide inhibitors (QZ59 compounds). The results indicated that two substitutions in transmembrane helix 6 reverse stereoselectivity of Sp-ABCB1a for QZ59 enantiomers compared with mouse ABCB1a. This suggests that subtle changes in the primary sequence of transporter drug binding domains could fine-tune substrate specificity through evolution. 相似文献
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Roux MM Townley IK Raisch M Reade A Bradham C Humphreys G Gunaratne HJ Killian CE Moy G Su YH Ettensohn CA Wilt F Vacquier VD Burke RD Wessel G Foltz KR 《Developmental biology》2006,300(1):416-433
The sea urchin egg has a rich history of contributions to our understanding of fundamental questions of egg activation at fertilization. Within seconds of sperm-egg interaction, calcium is released from the egg endoplasmic reticulum, launching the zygote into the mitotic cell cycle and the developmental program. The sequence of the Strongylocentrotus purpuratus genome offers unique opportunities to apply functional genomic and proteomic approaches to investigate the repertoire and regulation of Ca(2+) signaling and homeostasis modules present in the egg and zygote. The sea urchin "calcium toolkit" as predicted by the genome is described. Emphasis is on the Ca(2+) signaling modules operating during egg activation, but the Ca(2+) signaling repertoire has ramifications for later developmental events and adult physiology as well. Presented here are the mechanisms that control the initial release of Ca(2+) at fertilization and additional signaling components predicted by the genome and found to be expressed and operating in eggs at fertilization. The initial release of Ca(2+) serves to coordinate egg activation, which is largely a phenomenon of post-translational modifications, especially dynamic protein phosphorylation. Functional proteomics can now be used to identify the phosphoproteome in general and specific kinase targets in particular. This approach is described along with findings to date. Key outstanding questions regarding the activation of the developmental program are framed in the context of what has been learned from the genome and how this knowledge can be applied to functional studies. 相似文献
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Xu Q Schwarzenbacher R Krishna SS McMullan D Agarwalla S Quijano K Abdubek P Ambing E Axelrod H Biorac T Canaves JM Chiu HJ Elsliger MA Grittini C Grzechnik SK DiDonato M Hale J Hampton E Han GW Haugen J Hornsby M Jaroszewski L Klock HE Knuth MW Koesema E Kreusch A Kuhn P Miller MD Moy K Nigoghossian E Paulsen J Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J White A Wolf G Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2006,64(3):808-813
96.
Kemin Tan Alicia Sather Janice L. Robertson Shiu Moy Benoît Roux Andrzej Joachimiak 《Protein science : a publication of the Protein Society》2009,18(10):2043-2052
ZntB is the distant homolog of CorA Mg2+ transporter within the metal ion transporter superfamily. It was early reported that the ZntB from Salmonella typhimurium facilitated efflux of Zn2+ and Cd2+, but not Mg2+. Here, we report the 1.90 Å crystal structure of the intracellular domain of ZntB from Vibrio parahemolyticus. The domain forms a funnel-shaped homopentamer that is similar to the full-length CorA from Thermatoga maritima, but differs from two previously reported dimeric structures of truncated CorA intracellular domains. However, no Zn2+ or Cd2+ binding sites were identified in the high-resolution structure. Instead, 25 well-defined Cl− ions were observed and some of these binding sites are highly conserved within the ZntB family. Continuum electrostatics calculations suggest that the central pore of the funnel is highly attractive for cations, especially divalents. The presence of the bound Cl− ions increases the stability of cations along the pore suggesting they could be important in enhancing cation transport. 相似文献
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Joan Madurell-Malapeira David M. Alba Salvador Moyà-Solà Josep Aurell-Garrido 《Comptes Rendus Palevol》2010,9(1-2):55-62
Fossil puma-like cats (Puma pardoides) are recorded from several Late Pliocene to Early Pleistocene Eurasian localities, but the interpretation of the phylogenetic relationships between them and the extant puma (Puma concolor) remains controversial. In the past, extinct puma-like cats have been classified into several genera and species, and a close relationship with both pumas (Puma concolor) and snow leopards (Uncia uncia) has been suggested. Here, we describe the fossil remains of puma-like cats from the Iberian Peninsula. These remains (from the localities of La Puebla de Valverde, Cueva Victoria and Vallparadís) cover the whole known chronological distribution of this species in Eurasia. Although there are dentognathic similarities with U. uncia, the Iberian remains of P. pardoides most closely resemble the extant P. concolor. It is concluded that P. pardoides is closely related to living pumas, which supports a likely Eurasian origin of the puma lineage. 相似文献
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