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1.
H. R. Frischknecht B. Siegfried P. G. Waser 《Cellular and molecular life sciences : CMLS》1988,44(6):473-481
Summary Three animal models, based on genetic differences in endogenous opioid peptides and opioid receptors, are described. Obese mice and rats, whose pituitary opioid content is elevated, may be used to investigate eating disorders. Recombinant inbred strains of mice, which differ in brain opioid receptors and analgesic responsiveness, can be used for study of opioid-and nonopioid-mediated mechanisms of pain inhibition. Individual reactivity to opioids can be examined in C57BL/6 and DBA/2 inbred strains of mice. A model that combines a variety of opioid effects is offered and suggests the existence of a genetically determined dissociation of opioid effects on locomotor activity and pain inhibition. In addition, stimulatory locomotor responses in the C57BL/6 reaction type are linked to a high risk of drug addiction and facilitatory effects on adaptive processes, while high analgesic potency in the DBA/2 reaction type is accompanied by a low proneness to drug abuse and amnesic properties of opioids. 相似文献
2.
Three animal models, based on genetic differences in endogenous opioid peptides and opioid receptors, are described. Obese mice and rats, whose pituitary opioid content is elevated, may be used to investigate eating disorders. Recombinant inbred strains of mice, which differ in brain opioid receptors and analgesic responsiveness, can be used for study of opioid- and nonopioid-mediated mechanisms of pain inhibition. Individual reactivity to opioids can be examined in C57BL/6 and DBA/2 inbred strains of mice. A model that combines a variety of opioid effects is offered and suggests the existence of a genetically determined dissociation of opioid effects on locomotor activity and pain inhibition. In addition, stimulatory locomotor responses in the C57BL/6 reaction type are linked to a high risk of drug addiction and facilitatory effects on adaptive processes, while high analgesic potency in the DBA/2 reaction type is accompanied by a low proneness to drug abuse and amnesic properties of opioids. 相似文献
3.
Extracellular electron transfer 总被引:23,自引:0,他引:23
Results from several laboratories indicate that extracellular electron transfer may be a general mechanism whereby microoorganisms
generate energy for cell growth and/or maintenance. Specifically, bacteria can use redox-active organic small molecules, generated
outside or inside the cells, to shuttle electrons between reduced and oxidized compounds. Electron shuttling has now been
reported for several different bacterial species, and exchanges of shuttling compounds may even syntrophically link diverse
organisms in nature. Biofilm systems in both geological and clinical settings are likely to be important environments for
metabolisms that employ extracellular electron transfer. Both structural and functional analyses suggest that electron shuttles
and some virulence factors may be related to one another.
Received 21 March 2001; received after revision 10 May 2001; accepted 11 May 2001 相似文献
4.
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
5.
How do thermophilic proteins deal with heat? 总被引:9,自引:0,他引:9
Recent years have witnessed an explosion of sequence and structural information for proteins from hyperthermophilic and thermophilic
organisms. Complete genome sequences are available for many hyperthermophilic archaeons. Here, we review some recent studies
on protein thermostability along with work from our laboratory. A large number of sequence and structural factors are thought
to contribute toward higher intrinsic thermal stability of proteins from these organisms. The most consistent are surface
loop deletion, increased occurrence of hydrophobic residues with branched side chains and an increased proportion of charged
residues at the expense of uncharged polar residues. The energetic contribution of electrostatic interactions such as salt
bridges and their networks toward protein stability can be stabilizing or destabilizing. For hyperthermophilic proteins, the
contribution is mostly stabilizing. Macroscopically, improvement in electrostatic interactions and strengthening of hydrophobic
cores by branched apolar residues increase the enthalpy change between the folded and unfolded states of a thermophilic protein.
At the same time, surface loop deletion contributes to decreased conformational entropy and decreased heat capacity change
between the folded and unfolded states of the protein.
Received 28 February 2001; received after revision 26 March 2001; accepted 27 March 2001 相似文献
6.
Plasticins belong to the dermaseptin superfamily of gene-encoded, membrane-active host defense peptides produced by the skin
of hylid frogs. The plasticins, which are rich in Gly and Leu residues arranged in regular 5-mer motifs GXXXG (where X is
any amino acid residue), have very similar amino acid sequences, hydrophobicities, and amphipathicities but differ markedly
in their net charge, conformational plasticity, and activity spectra. The intrinsic flexibility and structural malleability
of plasticins modulate their ability to bind to and disrupt the membranes of prokaryotic and eukaryotic cells, and/or to reach
intracellular targets, therefore triggering functional versatility. This family of closely related but functionally divergent
peptides constitutes a good model to address the relationships between structural polymorphism, membrane-interacting properties,
and the biological activity of antimicrobial, cell-penetrating, and viral fusion peptides. Plasticins could thus serve as
templates to design potent multifunctional drugs that could act simultaneously against bacterial pathogens and viruses.
Received 26 September 2007; received after revision 22 October 2007; accepted 29 October 2007 相似文献
7.
CD23 (the low-affinity IgE receptor) as a C-type lectin: a multidomain and multifunctional molecule 总被引:5,自引:0,他引:5
Kijimoto-Ochiai S 《Cellular and molecular life sciences : CMLS》2002,59(4):648-664
This review, regards the low-affinity receptor CD23 as a C-type lectin and compares it with other C-type lectins and C-type
lectin-like receptors. C-type lectins such as the asialoglycoprotein receptor, as well as the dendritic cell immunoreceptor
and the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin on dendritic cell lectin, possess amino
acid sequences which interact with Ca++ and sugar, and many of them possess an endocytosis signal sequence that includes tyrosine or serine in the cytoplasmic region.
In contrast, natural killer receptors lack the Ca++ and sugar-binding amino acids but conserve homologous cysteines in the form of C-type lectin, and possess an immunoreceptor
tyrosine-based inhibitory motif in the cytoplasmic region which inhibits killer activity when they recognize the self major
histocompatibility (MHC) class I molecule. Since human CD23a form has a similar amino acid sequence, the possibility that
this sequence is an endocytosis signal or an ITIM is discussed. The function of the reverse RGD and RGD-binding inhibitory
peptide in human CD23 from the point of view of the relation between a C-type lectin and MHC class II molecules is also considered.
Received 21 May 2001; received after revision 28 November 2001; accepted 29 November 2001 相似文献
8.
Franciosi S 《Cellular and molecular life sciences : CMLS》2001,58(7):921-930
α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors are one type of ionotropic glutamate receptor involved
in rapid excitatory synaptic transmission. AMPA receptors have been increasingly implicated in long-term potentiation, and
recent evidence suggests that they may play a role in disorders affecting the nervous system. The finding that early in postnatal
development AMPA receptors are not expressed has lately been the focus of much attention. Resolving the factors involved in
AMPA receptor expression suggests that their induction is a developmentally regulated process with the possibility that alterations
in receptor expression may be correlated with pathology in neurological disorders. This paper provides an overview of factors
involved in AMPA receptor induction as well as of their role in plasticity and neuronal pathologies.
Received 5 December 2000; received after revision 12 January 2001; accepted 2 February 2001 相似文献
9.
Pharmacological versus binding analysis of receptor systems: how do they interplay? Myometrial cell receptors for oxytocin as a paradigm. 总被引:1,自引:0,他引:1
V Pliska 《Experientia》1991,47(3):216-221
Binding studies in various biological systems frequently indicate the presence of several binding sites for a biologically active ligand. They differ in their affinity for the ligand in question, binding capacity, and Hill coefficient, which suggests differences in the mechanisms of the binding site-ligand interactions. Identification of the 'true' receptors (sites initiating a cellular response) appears to be difficult. Three clusters of binding sites for oxytocin were found on rat myometrial cells. The oxytocin receptor seems to be linked to the medium-affinity site; the cooperation between the high- and medium-affinity sites in eliciting the uterotonic response seems likely, but lacks experimental proof. Dose-response analysis in partially irreversibly inhibited uterus preparations, the method of equipotent doses (Furchgott-Bursztyn method), and structure-activity analysis of oxytocin-like peptides acting as competitive inhibitors of oxytocin, turned out to be suitable for pharmacological analysis of this receptor system. 相似文献
10.
Sphingolipids in mammalian cell signalling 总被引:12,自引:0,他引:12
Sphingolipids and their metabolites, ceramide, sphingosine and sphingosine-1-phosphate, are involved in a variety of cellular
processes including differentiation, cellular senescence, apoptosis and proliferation. Ceramide is the main second messenger,
and is produced by sphingomyelinase-induced hydrolysis of sphingomyelin and by de novo synthesis. Many stimuli, e.g. growth
factors, cytokines, G protein-coupled receptor agonists and stress (UV irradiation) increase cellular ceramide levels. Sphingomyelin
in the plasma membrane is located primarily in the outer (extracellular) leaflet of the bilayer, whilst sphingomyelinases
are found at the inner (cytosolic) face and within lysosomes/endosomes. Such cellular compartmentalisation restricts the site
of ceramide production and subsequent interaction with target proteins. Glycosphingolipids and sphingomyelin together with
cholesterol are major components of specialised membrane microdomains known as lipid rafts, which are involved in receptor
aggregation and immune responses. Many signalling molecules, for example Src family tyrosine kinases and glycosylinositolphosphate-anchored
proteins, are associated with rafts, and disruption of these domains affects cellular responses such as apoptosis. Sphingosine
and sphingosine-1-phosphate derived from ceramide are also signalling molecules. In particular, sphingosine-1-phosphate is
involved in proliferation, differentiation and apoptosis. Sphingosine-1-phosphate can act both extracellularly through endothelial-differentiating
gene (EDG) family G protein-coupled receptors and intracellularly through direct interactions with target proteins. The importance
of sphingolipid signalling in cardiovascular development has been reinforced by recent reports implicating EDG receptors in
the regulation of embryonic cardiac and vascular morphogenesis.
Received 16 May 2001; received after revision 29 June 2001; accepted 3 July 2001 相似文献
11.
Waschek JA 《Cellular and molecular life sciences : CMLS》2004,61(18):2332-2342
The concept that atrial natriuretic peptide (ANP) and the closely related peptides BNP and CNP might be involved in the ontogeny of several organ systems emerged in the late 1980s. While many of the reported in vitro actions have not been examined in the context of organ development in vivo, recent studies demonstrate that mice which lack or overexpress natriuretic peptides or receptors exhibit pronounced skeletal growth defects. This article discusses how natriuretic peptides and other factors appear to regulate bone growth as an example of how natriuretic peptides might participate in the ontogeny of other organ systems. Evidence indicating that natriuretic peptides regulate neural development is then reviewed. Natriuretic peptides and receptors exhibit complex expression patterns in the developing nervous system, where they have been shown to act on neural cells as early as at the embryonic neural tube stage. Interestingly, both bone and brain growth appear to utilize primarily CNP and the CNP-specific type B receptor, and perhaps the type C receptor. In vitro data indicate that CNP may act on developing neurons, astrocytes and Schwann cells like a classical growth factor, regulating proliferation, patterning, phenotypic specification, survival and axonal pathfinding. Natriuretic peptides might also have roles in the vascularization of the embryonic brain, establishment of the blood-brain and blood-nerve barriers, and perhaps in nerve regeneration.Received 13 April 2004; received after revision 20 May 2004; accepted 27 May 2004 相似文献
12.
Melanocortin receptors: their functions and regulation by physiological agonists and antagonists 总被引:14,自引:0,他引:14
Abdel-Malek ZA 《Cellular and molecular life sciences : CMLS》2001,58(3):434-441
The melanocortins are a family of bioactive peptides derived from proopiomelanocortin, and share significant structural similarity.
Those peptides are best known for their stimulatory effects on pigmentation and steroidogenesis. Melanocortins are synthesized
in various sites in the central nervous system and in peripheral tissues, and participate in regulating multiple physiological
functions. Research during the past decade has provided evidence that melanocortins elicit their diverse biological effects
by binding to a distinct family of G protein-coupled receptors with seven transmembrane domains. To date, five melanocortin
receptor genes have been cloned and characterized. Those receptors differ in their tissue distribution and in their ability
to recognize the various melanocortins and the physiological antagonists, agouti signaling protein and agouti-related protein.
These advances have opened new horizons for exploring the significance of melanocortins, their antagonists, and their receptors
in a variety of important physiological functions.
Received 5 October 2000; accepted 10 November 2000 相似文献
13.
Bennasroune A Gardin A Auzan C Clauser E Dirrig-Grosch S Meira M Appert-Collin A Aunis D Crémel G Hubert P 《Cellular and molecular life sciences : CMLS》2005,62(18):2124-2131
Receptor tyrosine kinases play essential roles in cell proliferation and differentiation. We have recently shown that peptides corresponding to the transmembrane domains of the epidermal growth factor (EGF) and ErbB2 receptors inhibit their corresponding receptor activation in cancer cell lines. We extend this observation to cells transfected with chimeric insulin receptors where the transmembrane domain has been replaced by that of the EGF receptor or a mutated Erb2 domain. Peptides corresponding to the transmembrane domains of the EGF receptor and ErbB2 are able to inhibit specifically the autophosphorylation of insulin receptors with the corresponding domain. This inhibitory effect is correlated with the propensity of the different transmembrane domains to self-associate in a genetic reporter assay. Thus, our data strengthen the notion that transmembrane domains are involved in erbB receptor activation, and that these receptors can be modulated by inhibiting proteinprotein interactions within the membrane.Received 25 May 2005; received after revision 13 July 2005; accepted 22 July 2005 相似文献
14.
The receptors for regulatory peptides have been extensively characterized using radioligand binding techniques. By combining these binding techniques with autoradiography it is possible to visualize at the light and electron microscopic levels the anatomical and cellular localization of these receptors. In this review we discuss the procedures used to label peptide receptors for autoradiography and the peculiarities of peptides as ligands. The utilization of autoradiography in mapping peptide receptors in brain and peripheral tissues, some of the new insights revealed by these studies particularly the problem of 'mismatch' between endogenous peptides and receptors, the existence of multiple receptors for a given peptide family and the use of peptide receptor autoradiography in human tissues are also reviewed. 相似文献
15.
Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding
protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding
of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and
single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing
of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism
of amyloid formation and detecting the variant gene in individuals at risk.
Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001 相似文献
16.
H. Van Dael 《Cellular and molecular life sciences : CMLS》1998,54(11):1217-1230
Protein folding is an extremely active field of research where biology, chemistry, computer science and physics meet. Although
the study of protein-folding intermediates in general and equilibrium intermediates in particular has grown considerably in
recent years, many questions regarding the conformational state and the structural features of the various partially folded
intermediate states remain unanswered. Performing kinetic measurements on proteins that have had their structures modified
by site-directed mutagenesis, the so-called protein-engineering method, is an obvious way to gain fine structural information.
In the present review, this method has been applied to a variety of proteins belonging to the lysozyme/α-lactalbumin family. Besides recombinants obtained by point mutations of individual critical residues, chimeric proteins in
which whole structural elements (10 – 25 residues) from α-lactalbumin were inserted into a human lysozyme matrix are examined. The conformational properties of the equilibrium intermediate
states are discussed together with the structural characterization of the partially unfolded states encountered in the kinetic
folding pathway.
Received 28 May 1998; received after revision 6 July 1998; accepted 6 July 1998 相似文献
17.
18.
Yi CS Song YS Ryu KS Sohn J Ji I Ji TH 《Cellular and molecular life sciences : CMLS》2002,59(6):932-940
The gonadotropin receptors are G-protein-coupled receptors with unique structural and functional features, consisting of
two halves. The N-terminal extracellular half (exodomain) binds the hormones, whereas the C-terminal membrane-associated half
(endodomain) is responsible for receptor activation. In this review, the novel ternary interactions, contact points and mutual
modulations among the exodomain, endodomain and hormone for hormone binding and signal generation are described based on the
latest observations. This discussion is contrary to the view that the exodomain and endodomain are independent, at least functionally,
and provides new insights into the receptor mechanisms for the gonadotropins and other G-protein-coupled receptors.
Received 7 November 2001; received after revision 2 January 2002; accepted 3 January 2002 相似文献
19.
The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease 总被引:16,自引:0,他引:16
Nijtmans LG Artal SM Grivell LA Coates PJ 《Cellular and molecular life sciences : CMLS》2002,59(1):143-155
Although originally identified as putative negative regulators of the cell cycle, recent studies have demonstrated that the
PHB proteins act as a chaperone in the assembly of subunits of mitochondrial respiratory chain complexes. The two PHB proteins,
Phb1p and Phb2p, are located in the mitochondrial inner membrane where they form a large complex that represents a novel type
of membrane-bound chaperone. On the basis of its native molecular weight, the PHB-complex should contain 12-14 copies of both
Phb1p and Phb2p. The PHB complex binds directly to newly synthesised mitochondrial translation products and stabilises them
against degradation by membrane-bound metalloproteases belonging to the family of mitochondrial triple-A proteins. Sequence
homology assigns Phb1p and Phb2p to a family of proteins which also contains stomatins, HflKC, flotillins and plant defence
proteins. However, to date only the bacterial HflKC proteins have been shown to possess a direct functional homology with
the PHB complex. Previously assigned actions of the PHB proteins, including roles in tumour suppression, cell cycle regulation,
immunoglobulin M receptor binding and apoptosis seem unlikely in view of any hard evidence in their support. Nevertheless,
because the proteins are probably indirectly involved in ageing and cancer, we assess their possible role in these processes.
Finally, we suggest that the original name for these proteins, the prohibitins, should be amended to reflect their roles as
proteins that hold badly formed subunits, thereby keeping the nomenclature already in use but altering its meaning to reflect
their true function more accurately.
Received 21 May 2001; received after revision 2 July 2001; accepted 24 July 2001 相似文献
20.
Amyloid β-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin 总被引:1,自引:0,他引:1
The accumulation of aggregates of amyloidogenic peptides is associated with numerous human diseases. One well studied example is the association between deposition of amyloid beta (Abeta) and Alzheimer's disease. Insulin degrading enzyme and neprilysin are involved in the clearance of Abeta, and presequence peptidase is suggested to play a role in the degradation of mitochondrial Abeta. Recent structural analyses reveal that these three peptidases contain a catalytic chamber (crypt) that selectively encapsulates and cleaves amyloidogenic peptides, hence the name cryptidase. The substrate selectivity of these cryptidases is determined by the size and charge distribution of their crypt as well as the conformational flexibility of substrates. The interaction of Abeta with the catalytic core of these cryptidases is controlled by conformational changes that make the catalytic chambers accessible for Abeta binding. These new structural and biochemical insights into cryptidases provide potential therapeutic strategies for the control of Abeta clearance. 相似文献