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1.
Regulation of plant ferritin synthesis: how and why 总被引:9,自引:0,他引:9
Briat JF Lobréaux S Grignon N Vansuyt G 《Cellular and molecular life sciences : CMLS》1999,56(1-2):155-166
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Martina Giannaccini Alice Usai Federica Chiellini Viviana Guadagni Massimiliano Andreazzoli Michela Ori Massimo Pasqualetti Luciana Dente Vittoria Raffa 《Cellular and molecular life sciences : CMLS》2018,75(7):1255-1267
Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy. 相似文献
3.
Matthew D. Hitchings Philip Townsend Ehmke Pohl Paul D. Facey D. Hugh Jones Paul J. Dyson Ricardo Del Sol 《Cellular and molecular life sciences : CMLS》2014,71(24):4911-4926
Dps proteins are members of an extensive family of proteins that oxidise and deposit iron in the form of ferric oxide, and are also able to bind DNA. Ferroxidation centres are formed at the interface of anti-parallel dimers, which further assemble into dodecameric nanocages with a hollow core where ferric oxide is deposited. Streptomyces coelicolor encodes three Dps-like proteins (DpsA, B and C). Despite sharing the conserved four-helix bundle organisation observed in members of the Dps family, they display significant differences in the length of terminal extensions, or tails. DpsA possess both N- and C-terminal tails of different lengths, and their removal affects quaternary structure assembly to varying degrees. DpsC quaternary structure, on the other hand, is heavily dependent on its N-terminal tail as its removal abolishes correct protein folding. Analysis of the crystal structure of dodecamers from both proteins revealed remarkable differences in the position of tails and interface surface area; and provides insight to explain the differences in biochemical behaviour observed while comparing DpsA and DpsC. 相似文献
4.
Hjalte Holm Andersen Kasper Bendix Johnsen Torben Moos 《Cellular and molecular life sciences : CMLS》2014,71(9):1607-1622
Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS. 相似文献
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Bruno Mesmin Bruno Antonny Guillaume Drin 《Cellular and molecular life sciences : CMLS》2013,70(18):3405-3421
In cells, the levels of sterol vary greatly among organelles. This uneven distribution depends largely on non-vesicular routes of transfer, which are mediated by soluble carriers called lipid-transfer proteins (LTPs). These proteins have a domain with a hydrophobic cavity that accommodates one sterol molecule. However, a demonstration of their role in sterol transport in cells remains difficult. Numerous LTPs also contain membrane-binding elements, but it is not clear how these LTPs couple their ability to target organelles with lipid transport activity. This issue appears critical, since many sterol transporters are thought to act at contact sites between two membrane-bound compartments. Here, we emphasize that biochemical and structural studies provide precious insights into the mode of action of sterol-binding proteins. Recent studies on START, Osh/ORP and NPC proteins suggest models on how these proteins could transport sterol between organelles and, thereby, influence cellular functions. 相似文献
7.
Prochownik EV 《Cellular and molecular life sciences : CMLS》2005,62(21):2438-2459
The discovery of oncogenes (c-onc’s) and tumor suppressors (TS’s) has led to the concept that cancer arises from defects in
each of these classes of genes or their products. More recently, it has been appreciated that c-onc and TS proteins often
affect one another’s functions. Within this context, I review the two classical TS’s, p53 and the retinoblastoma protein,
and the consequences of their inactivation. The various forms of genomic instability (GI) that underly the high mutation rates
of transformed cells are then discussed. Particular emphasis is placed upon the concept that GI is not only an integral part
of the transformed state but is a prerequisite. Increased oxidative DNA damage, and/or an inabiliy to repair it, can lead
to GI. The review then discusses recent observations showing that loss of the TS protein peroxiredoxin 1 (prdx1) and increased
expression of the c-onc protein c-Myc, each leads to increased oxidative DNA damage. The critical nature of the c-onc-TS interaction
is underscored by that occurring between prdx1 and c-Myc, with the former protein regulating the production of DNA-damaging
reactive oxygen species by the latter. The intimate association between these proteins and others serves as a paradigm for
the exquisite balancing act that c-onc’s and TS’s must maintain in order to properly control normal DNA replication and cellular
proliferation while simultaneously minimizing the acquisition of potentially neoplastic mutations.
Received 10 May 2005; received after revision 3 July 2005; accepted 19 July 2005 相似文献
8.
A dynamic view of peptides and proteins in membranes 总被引:1,自引:0,他引:1
Bechinger B 《Cellular and molecular life sciences : CMLS》2008,65(19):3028-3039
Biological membranes are highly dynamic supramolecular arrangements of lipids and proteins, which fulfill key cellular functions.
Relatively few high-resolution membrane protein structures are known to date, although during recent years the structural
databases have expanded at an accelerated pace. In some instances the structures of reaction intermediates provide a stroboscopic
view on the conformational changes involved in protein function. Other biophysical approaches add dynamic aspects and allow
one to investigate the interactions with the lipid bilayers. Membrane-active peptides fulfill many important functions in
nature as they act as antimicrobials, channels, transporters or hormones, and their studies have much increased our understanding
of polypeptide-membrane interactions. Interestingly several proteins have been identified that interact with the membrane
as loose arrays of domains. Such conformations easily escape classical high-resolution structural analysis and the lessons
learned from peptides may therefore be instructive for our understanding of the functioning of such membrane proteins.
Received 11 March 2008; received after revision 2 May 2008; accepted 5 May 2008 相似文献
9.
Sagane Y Hosp J Zech K Thompson EM 《Cellular and molecular life sciences : CMLS》2011,68(9):1611-1622
Oriented cellulose deposition is critical to plant patterning and models suggest microtubules constrain cellulose synthase
movements through the plasma membrane. Though widespread in plants, urochordates are the only animals that synthesize cellulose.
We characterized the distinctive cellulose microfibril scaffold of the larvacean house and its interaction with house structural
proteins (oikosins). Targeted disruption of cytoskeletal elements, secretory pathways, and plasma membrane organization, suggested
a working model for templating extracellular cellulose microfibrils from animal cells that shows both convergence and differences
to plant models. Specialized cortical F-actin arrays template microfibril orientation and glycosylphosphatidylinositol-anchored
proteins in lipid rafts may act as scaffolding proteins in microfibril elongation. Microtubules deliver and maintain cellulose
synthase complexes to specific cell membrane sites rather than orienting their movement through the membrane. Oikosins are
incorporated into house compartments directly above their corresponding cellular field of expression and interact with the
cellulose scaffold to a variable extent. 相似文献
10.
BAR domain superfamily proteins have emerged as central regulators of dynamic membrane remodeling, thereby playing important
roles in a wide variety of cellular processes, such as organelle biogenesis, cell division, cell migration, secretion, and
endocytosis. Here, we review the mechanistic and structural basis for the membrane curvature-sensing and deforming properties
of BAR domain superfamily proteins. Moreover, we summarize the present state of knowledge with respect to their regulation
by autoinhibitory mechanisms or posttranslational modifications, and their interactions with other proteins, in particular
with GTPases, and with membrane lipids. We postulate that BAR superfamily proteins act as membrane-deforming scaffolds that
spatiotemporally orchestrate membrane remodeling. 相似文献
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Immunological properties of oxygen-transport proteins: hemoglobin,hemocyanin and hemerythrin 总被引:2,自引:0,他引:2
It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dynamics in innate immunity, and to impress upon the reader the multi-functionality of these ancient proteins on the basis of their structures. In this context, erythrocyte–pathogen antibiosis and the immune competences of various erythroid cells are compared across diverse taxa. 相似文献
13.
Defining a neuron: neuronal ELAV proteins 总被引:1,自引:1,他引:0
Neuronal cells strongly depend on the control exerted by RNA-binding proteins (RBPs) on gene expression for the establishment
and maintenance of their phenotype. Neuronal ELAV (nELAV) proteins are RBPs able to influence virtually every aspect of the
postsynthesis fate of bound mRNAs, from polyadenylation, alternative splicing and nuclear export to cytoplasmic localization,
stability and translation. They enhance gene expression through the last two, best documented activities, increasing mRNA
half-life and promoting protein synthesis by a still-unknown molecular mechanism. Developmentally, nELAV proteins have been
shown to act as inducers of the transition between neural stem/progenitor cells and differentiation-committed cells, also
assisting these neuroblasts in the completion of their maturation program. In brain physiology, they are also the first RBPs
demonstrated to have a pivotal role in memory, where they probably control mRNA availability for translation in subcellular
domains, thereby providing a biochemical means for selective increase in synaptic strength.
Received 15 January 2007; received after revision 10 August 2007; accepted 6 September 2007 相似文献
14.
Alcohols affect a wide array of biological processes including protein folding, neurotransmission and immune responses. It is becoming clear that many of these effects are mediated by direct binding to proteins such as neurotransmitter receptors and signaling molecules. This review summarizes the unique chemical properties of alcohols which contribute to their biological effects. It is concluded that alcohols act mainly as hydrogen bond donors whose binding to the polypeptide chain is stabilized by hydrophobic interactions. The electronegativity of the O atom may also play a role in stabilizing contacts with the protein. Properties of alcohol binding sites have been derived from X-ray crystal structures of alcohol-protein complexes and from mutagenesis studies of ion channels and enzymes that bind alcohols. Common amino acid sequences and structural features are shared among the protein segments that are involved in alcohol binding. The alcohol binding site is thought to consist of a hydrogen bond acceptor in a turn or loop region that is often situated at the N-terminal end of an alpha-helix. The methylene chain of the alcohol molecule appears to be accommodated by a hydrophobic groove formed by two or more structural elements, frequently a turn and an alpha-helix. Binding at these sites may alter the local protein structure or displace bound solvent molecules and perturb the function of key proteins. 相似文献
15.
Laitinen OH Hytönen VP Nordlund HR Kulomaa MS 《Cellular and molecular life sciences : CMLS》2006,63(24):2992-3017
Chicken avidin and bacterial streptavidin, (strept)avidin, are proteins widely utilized in a number of applications in life
science, ranging from purification and labeling techniques to diagnostics, and from targeted drug delivery to nanotechnology.
(Strept)avidin-biotin technology relies on the extremely tight and specific affinity between (strept)avidin and biotin (dissociation
constant, Kd≈10−14–10−16 M). (Strept)avidins are also exceptionally stable proteins. To study their ligand binding and stability characteristics,
the two proteins have been extensively modified both chemically and genetically. There are excellent accounts of this technology
and chemically modified (strept)avidins, but no comprehensive reviews exist concerning genetically engineered (strept)avidins.
To fill this gap, we here go through the genetically engineered (strept)avidins, summarizing how these constructs were designed
and how they have improved our understanding of the structural and functional characteristics of these proteins, and the benefits
they have provided for (strept)avidin-biotin technology.
Received 22 June 2006; received after revision 1 August 2006; accepted 21 September 2006 相似文献
16.
Glycine-rich proteins as structural components of plant cell walls 总被引:12,自引:0,他引:12
Glycine-rich proteins (GRPs) have been found in the cell walls of many higher plants and form a third group of structural
protein components of the wall in addition to extensins and proline-rich proteins. The primary sequences of GRPs contain more
than 60% glycine. GRPs are localized mainly in the vascular tissue of the plant, and their coding genes provide an excellent
system to analyze the molecular basis of vascular-specific gene expression. In French bean, the major cell wall GRP has been
localized at the ultrastructural level in the modified primary cell wall of protoxylem. Immunological studies showed that
it forms a major part of these highly extensible and specialized cell walls. Specific digestion of GRP1.8 from bean by collagenase
suggests that it shares structural similarities with collagen. The protein is synthesized by living protoxylem cells as well
as xylem parenchyma cells. After cell death, GRPs are exported from neighboring xylem parenchyma cells to the protoxylem wall,
a rare example of protein transport between cells in plants. We propose that GRPs are part of a repair system of the plant
during the stretching phase of protoxylem. 相似文献
17.
Thyroid hormone-induced oxidative stress 总被引:6,自引:0,他引:6
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Y. Aron M. Vayssier-Taussat M. Bachelet B.S. Polla 《Cellular and molecular life sciences : CMLS》2001,58(10):1522-1527
The anti-ulcer drug geranylgeranylacetone (GGA) has been shown to induce the expression of heat shock proteins (HSPs), in particular of Hsp70, in gastric and small intestine cells. In this study, we investigated whether GGA was able to induce Hsp70 in another cell type, human monocytes, which represent a well-established model of Hsp70 expression under oxidative stress. In these cells, GGA had no significant effect either on basal or tobacco smoke-induced Hsp70 expression. We further investigated the effects of GGA on mitochondria, a key organelle of oxidant-mediated cell injury and a putative target for GGA-mediated protection. GGA significantly increased basal mitochondrial membrane polarization and inhibited the decrease in mitochondrial membrane potential of human monocytes exposed to distinct sources of clinically relevant oxidants such as tobacco smoke and y-irradiation. Our results indicate that mitochondria are targets for GGA-mediated protection against oxidative stress in human monocytes, independently of Hsp70. 相似文献