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121.
Molecular basis of guanine nucleotide dissociation inhibitor activity of human neuroglobin by chemical cross-linking and mass spectrometry 总被引:1,自引:0,他引:1
Kitatsuji C Kurogochi M Nishimura S Ishimori K Wakasugi K 《Journal of molecular biology》2007,368(1):150-160
Oxidized human neuroglobin (Ngb), a heme protein expressed in the brain, has been proposed to act as a guanine nucleotide dissociation inhibitor (GDI) for the GDP-bound form of the heterotrimeric G protein alpha-subunit (Galpha(i)). Here, to elucidate the molecular mechanism underlying the GDI activity of Ngb, we used an glutathione-S-transferase pull-down assay to confirm that Ngb competes with G-protein betagamma-subunits (Gbetagamma) for binding to Galpha(i), and identified the Galpha(i)-binding site in Ngb by chemical cross-linking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and sulfo-N-hydroxysuccinimide, coupled with mass spectrometry (MS). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis for tryptic peptides derived from the cross-linked Ngb-Galpha(i) complex revealed several binding regions in Ngb. Furthermore, MALDI-TOF/TOF MS analysis of the cross-linked Ngb and Galpha(i) peptides, together with the MS/MS scoring method, predicted cross-linking between Glu60 (Ngb) and Ser206 (Galpha(i)), and between Glu53 (Ngb) and Ser44 (Galpha(i)). Because Ser206 of Galpha(i) is located in the region that contacts Gbetagamma, binding of Ngb could facilitate the release of Gbetagamma from Galpha(i). Binding of Ngb to Galpha(i) would also inhibit the exchange of GDP for GTP, because Ser44 (Galpha(i)) is adjacent to the GDP-binding site and Glu53 (Ngb), which is cross-linked to Ser44 (Galpha(i)), could be located close to GDP. Thus, we have identified, for the first time, the sites of interaction between Ngb and Galpha(i), enabling us to discuss the functional significance of this binding on the GDI activity of Ngb. 相似文献
122.
The human olfactory subgenome has recently been fully characterized with over 1000 genes. Although as many as two thirds of them are expected to be pseudogenes, it still leaves us with about half of all human G protein-coupled receptors being olfactory. It is therefore of great interest to characterize olfactory receptors with high precision. Usually it is done through sequence motifs that are not fully conserved, making an exact characterization difficult. In this paper, we propose a rule-based characterization of olfactory receptors derived from a multiple sequence alignment of human GPCRs. We show that just seven alignment sites are sufficient to characterize 99% of human olfactory GPCRs with one feature, a tyrosine at site 7.41, being of particular importance. We also show dependencies between sites near the extracellular and intracellular region of a membrane-embedded receptor, indicating that olfactory receptors are characterized by a combination of important residues in these two areas, whereas nonolfactory receptors tend to have residues of lower importance at the same sites. 相似文献
123.
The motif prediction problem is to predict short, conserved subsequences that are part of a family of sequences, and it is a very important biological problem. Gibbs is one of the first successful motif algorithms and it runs very fast compared with other algorithms, and its search behavior is based on the well-studied Gibbs random sampling. However, motif prediction is a very difficult problem and Gibbs may not predict true motifs in some cases. Thus, the authors explored a possibility of improving the prediction accuracy of Gibbs while retaining its fast runtime performance. In this paper, the authors considered Gibbs only for proteins, not for DNA binding sites. The authors have developed iGibbs, an integrated motif search framework for proteins that employs two previous techniques of their own: one for guiding motif search by clustering sequences and another by pattern refinement. These two techniques are combined to a new double clustering approach to guiding motif search. The unique feature of their framework is that users do not have to specify the number of motifs to be predicted when motifs occur in different subsets of the input sequences since it automatically clusters input sequences into clusters and predict motifs from the clusters. Tests on the PROSITE database show that their framework improved the prediction accuracy of Gibbs significantly. Compared with more exhaustive search methods like MEME, iGibbs predicted motifs more accurately and runs one order of magnitude faster. 相似文献
124.
Riemann M Gutjahr C Korte A Riemann M Danger B Muramatsu T Bayer U Waller F Furuya M Nick P 《Plant biology (Stuttgart, Germany)》2007,9(1):32-40
The reaction of the rice mutant HEBIBA differs from that of wild-type rice in that the mutant responds inversely to red light and is defective in the light-triggered biosynthesis of jasmonic acid (JA). Using the wild type and the HEBIBA mutant of rice in a differential display screen, we attempted to identify genes that act in or near the convergence point of light and JA signalling. We isolated specifically regulated DNA fragments from approximately 10 000 displayed bands, and identified a new early light- and JA-induced gene. This gene encodes an enzyme containing a GDSL motif, showing 38 % identity at the amino acid level to lipase Arab-1 in Arabidopsis thaliana. The GDSL CONTAINING ENZYME RICE 1 gene (GER1) is rapidly induced by both red (R) and far-red (FR) light and by JA. The results are discussed with respect to a possible role for GER1 as a negative regulator of coleoptile elongation in the context of recent findings on the impact of JA on light signalling. 相似文献
125.
Xuejun C. Zhang Yan Zhao Jie Heng Daohua Jiang 《Protein science : a publication of the Protein Society》2015,24(10):1560-1579
Major facilitator superfamily (MFS) is a large class of secondary active transporters widely expressed across all life kingdoms. Although a common 12‐transmembrane helix‐bundle architecture is found in most MFS crystal structures available, a common mechanism of energy coupling remains to be elucidated. Here, we discuss several models for energy‐coupling in the transport process of the transporters, largely based on currently available structures and the results of their biochemical analyses. Special attention is paid to the interaction between protonation and the negative‐inside membrane potential. Also, functional roles of the conserved sequence motifs are discussed in the context of the 3D structures. We anticipate that in the near future, a unified picture of the functions of MFS transporters will emerge from the insights gained from studies of the common architectures and conserved motifs. 相似文献
126.
Biomimetic repeat protein derived from Xenopus tropicalis for fibrous scaffold fabrication 下载免费PDF全文
Yunkyeoung Kwon Yun Jung Yang Dooyup Jung Byeong Hee Hwang Hyung Joon Cha 《Biopolymers》2015,103(12):659-664
Collagen, silk, and elastin are the fibrous proteins consist of representative amino acid repeats. Because these proteins exhibited distinguishing mechanical properties, they have been utilized in diverse applications, such as fiber‐based sensors, filtration membranes, supporting materials, and tissue engineering scaffolds. Despite their infinite prevalence and potential, most studies have only focused on a few repeat proteins. In this work, the hypothetical protein with a repeat motif derived from the frog Xenopus tropicalis was obtained and characterized for its potential as a novel protein‐based material. The codon‐optimized recombinant frog repeat protein, referred to as ‘xetro’, was produced at a high rate in a bacterial system, and an acid extraction‐based purified xetro protein was successfully fabricated into microfibers and nanofibers using wet spinning and electrospinning, respectively. Specifically, the wet‐spun xetro microfibers demonstrated about 2‐ and 1.5‐fold higher tensile strength compared with synthetic polymer polylactic acid and cross‐linked collagen, respectively. In addition, the wet‐spun xetro microfibers showed about sevenfold greater stiffness than collagen. Therefore, the mass production potential and greater mechanical properties of the xetro fiber may result in these fibers becoming a new promising fiber‐based material for biomedical engineering. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 659–664, 2015. 相似文献
127.
The Drosophila type I transmembrane protein Crumbs is an apical determinant required for the maintenance of apico‐basal epithelial cell polarity. The level of Crumbs at the plasma membrane is crucial, but how it is regulated is poorly understood. In a genetic screen for regulators of Crumbs protein trafficking we identified Sar1, the core component of the coat protein complex II transport vesicles. sar1 mutant embryos show a reduced plasma membrane localization of Crumbs, a defect similar to that observed in haunted and ghost mutant embryos, which lack Sec23 and Sec24CD, respectively. By pulse‐chase assays in Drosophila Schneider cells and analysis of protein transport kinetics based on Endoglycosidase H resistance we identified an RNKR motif in Crumbs, which contributes to efficient ER export. The motif identified fits the highly conserved di‐basic RxKR motif and mediates interaction with Sar1. The RNKR motif is also required for plasma membrane delivery of transgene‐encoded Crumbs in epithelial cells of Drosophila embryos. Our data are the first to show that a di‐basic motif acts as a signal for ER exit of a type I plasma membrane protein in a metazoan organism. 相似文献
128.
129.
Wang MM 《The international journal of biochemistry & cell biology》2011,43(11):1550-1562
Originally discovered nearly a century ago, the Notch signaling pathway is critical for virtually all developmental programs and modulates an astounding variety of pathogenic processes. The DSL (Delta, Serrate, LAG-2 family) proteins have long been considered canonical activators of the core Notch pathway. More recently, a wide and expanding network of non-canonical extracellular factors has also been shown to modulate Notch signaling, conferring newly appreciated complexity to this evolutionarily conserved signal transduction system. Here, I review current concepts in Notch signaling, with a focus on work from the last decade elucidating novel extracellular proteins that up- or down-regulate signal potency. 相似文献
130.
Jelcic I Reichel J Schlude C Treutler E Sinzger C Steinle A 《Traffic (Copenhagen, Denmark)》2011,12(10):1444-1456
Human cytomegalovirus (HCMV) is a widespread and persistent beta-herpesvirus. The large DNA genome of HCMV encodes many proteins that are non-essential for viral replication including numerous proteins subverting host immunosurveillance. One of them is the barely characterized UL20, which is encoded adjacent to the well-defined immunoevasins UL16 and UL18. UL20 is a type I transmembrane glycoprotein with an immunoglobulin-like ectodomain that is highly polymorphic among HCMV strains. Here, we show that the homodimeric UL20, by virtue of its cytoplasmic domain, does not reach the cell surface but is targeted to endosomes and lysosomes. Accordingly, UL20 exhibits a short half-life because of rapid lysosomal degradation. Trafficking of UL20 to lysosomes is determined by several, independently functioning dileucine-based sorting motifs in the cytoplasmic domain of UL20 and involves the adaptor protein (AP) complex AP-1. Combined substitution of three dileucine motifs allowed strong cell surface expression of UL20 comparable to UL20 mutants lacking the cytoplasmic tail. Finally, we show that the intracellularly located UL20 also is subject to lysosomal degradation in the context of viral infection. Altogether, from these data, we hypothesize that UL20 is destined to efficiently sequester yet-to-be defined cellular proteins for degradation in lysosomes. 相似文献