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1.
In 1905, Albert Einstein proposed that the forces that cause the random Brownian motion of a particle also underlie the resistance
to macroscopic motion when a force is applied. This insight, of a coupling between fluctuation (stochastic behavior) and responsiveness
(non-stochastic behavior), founded an important branch of physics. Here we argue that his insight may also be relevant for
understanding evolved biological systems, and we present a ‘fluctuation–response relationship’ for biology. The relationship
is consistent with the idea that biological systems are similarly canalized to stochastic, environmental, and genetic perturbations.
It is also supported by in silico evolution experiments, and by the observation that ‘noisy’ gene expression is often both
more responsive and more ‘evolvable’. More generally, we argue that in biology there is (and always has been) an important
role for macroscopic theory that considers the general behavior of systems without concern for their intimate molecular details. 相似文献
2.
M. V. Nogués M. Moussaoui E. Boix M. Vilanova M. Ribó C. M. Cuchillo 《Cellular and molecular life sciences : CMLS》1998,54(8):766-774
The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment
between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases,
enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and
basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in
the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized
by structural and kinetic studies. In addition to the active site (p1 ), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been
proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3′ side and 5′ side, respectively,
of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2 , and Lys-66 in p0 ) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A.
The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA. 相似文献
3.
Zinkernagel RM 《Cellular and molecular life sciences : CMLS》2012,69(10):1635-1640
So-called ‘immunological memory’ is, in my view, a typical example where a field of enquiry, i.e. to understand long-term
protection to survive reexposure to infection, has been overtaken by ‘l’art pour l’art’ of ‘basic immunology’. The aim of
this critical review is to point out some key differences between academic text book-defined immunological memory and protective
immunity as viewed from a co-evolutionary point of view, both from the host and the infectious agents. A key conclusion is
that ‘immunological memory’ of course exists, but only in particular experimental laboratory models measuring ‘quicker and
better’ responses after an earlier immunization. These often do correlate with, but are not the key mechanisms of, protection.
Protection depends on pre-existing neutralizing antibodies or pre-activated T cells at the time of infection—as documented
by the importance of maternal antibodies around birth for survival of the offspring. Importantly, both high levels of antibodies
and of activated T cells are antigen driven. This conclusion has serious implications for our thinking about vaccines and
maintaining a level of protection in the population to deal with old and new infectious diseases. 相似文献
4.
How a conformationally disordered polypeptide chain rapidly and efficiently achieves its well-defined native structure is
still a major question in modern structural biology. Although much progress has been made towards rationalizing the principles
of protein structure and dynamics, the mechanism of the folding process and the determinants of the final fold are not yet
known in any detail. One protein for which folding has been studied in great detail by a combination of diverse techniques
is hen lysozyme. In this article we review the present state of our knowledge of the folding process of this enzyme and focus
in particular on recent experiments to probe some of its specific features. These results are then discussed in the context
of the ‘new view’ of protein folding based on energy surfaces and land scapes. It is shown that a schematic energy surface
for lysozyme folding, which is broadly consistent with our experimental data, begins to provide a unified model for protein
folding through which experimental and theoretical ideas can be brought together. 相似文献
5.
Although its operations are not limited to the spatial domain, there is a near consensus that the hippocampus plays a critical
role in memory for place. This review aims to explore this role, with a particular emphasis on the functions performed by
distinct hippocampal subregions. The use of innovative lesioning techniques, localized pharmacological treatments, and molecular
genetic interventions is offering increasingly precise brain-regional specificity and temporal control. Together with the
electrophysiological recording of neuronal activity, these techniques are beginning to shed light on the functioning of specific
components of the hippocampal circuitry in the different phases of memory – encoding, storage, consolidation, and retrieval.
In view of these developments, we examine the involvement of the hippocampus in the encoding versus retrieval of spatial memory,
before turning to the issue of long-term information storage and the role of ‘cellular’ and ‘systems’ consolidation processes
in the formation of lasting memories.
Received 17 July 2006; received after revision 24 October 2006; accepted 16 November 2006 相似文献
6.
The application of fractal dimension-based constructs to probe the protein interior dates back to the development of the concept
of fractal dimension itself. Numerous approaches have been tried and tested over a course of (almost) 30 years with the aim
of elucidating the various facets of symmetry of self-similarity prevalent in the protein interior. In the last 5 years especially,
there has been a startling upsurge of research that innovatively stretches the limits of fractal-based studies to present
an array of unexpected results on the biophysical properties of protein interior. In this article, we introduce readers to
the fundamentals of fractals, reviewing the commonality (and the lack of it) between these approaches before exploring the
patterns in the results that they produced. Clustering the approaches in major schools of protein self-similarity studies,
we describe the evolution of fractal dimension-based methodologies. The genealogy of approaches (and results) presented here
portrays a clear picture of the contemporary state of fractal-based studies in the context of the protein interior. To underline
the utility of fractal dimension-based measures further, we have performed a correlation dimension analysis on all of the
available non-redundant protein structures, both at the level of an individual protein and at the level of structural domains.
In this investigation, we were able to separately quantify the self-similar symmetries in spatial correlation patterns amongst
peptide–dipole units, charged amino acids, residues with the π-electron cloud and hydrophobic amino acids. The results revealed
that electrostatic environments in the interiors of proteins belonging to ‘α/α toroid’ (all-α class) and ‘PLP-dependent transferase-like’
domains (α/β class) are highly conducive. In contrast, the interiors of ‘zinc finger design’ (‘designed proteins’) and ‘knottins’
(‘small proteins’) were identified as folds with the least conducive electrostatic environments. The fold ‘conotoxins’ (peptides)
could be unambiguously identified as one type with the least stability. The same analyses revealed that peptide–dipoles in
the α/β class of proteins, in general, are more correlated to each other than are the peptide–dipoles in proteins belonging
to the all-α class. Highly favorable electrostatic milieu in the interiors of TIM-barrel, α/β-hydrolase structures could explain
their remarkably conserved (evolutionary) stability from a new light. Finally, we point out certain inherent limitations of
fractal constructs before attempting to identify the areas and problems where the implementation of fractal dimension-based
constructs can be of paramount help to unearth latent information on protein structural properties. 相似文献
7.
Alastair S. Robertson Elizabeth Smythe Kathryn R. Ayscough 《Cellular and molecular life sciences : CMLS》2009,66(13):2049-2065
Endocytosis is a fundamental eukaryotic process required for remodelling plasma-membrane lipids and protein to ensure appropriate
membrane composition. Increasing evidence from a number of cell types reveals that actin plays an active, and often essential,
role at key endocytic stages. Much of our current mechanistic understanding of the endocytic process has come from studies
in budding yeast and has been facilitated by yeast’s genetic amenability and by technological advances in live cell imaging.
While endocytosis in metazoans is likely to be subject to a greater array of regulatory signals, recent reports indicate that
spatiotemporal aspects of vesicle formation requiring actin are likely to be conserved across eukaryotic evolution. In this
review we focus on the ‘modular’ model of endocytosis in yeast before highlighting comparisons with other cell types. Our
discussion is limited to endocytosis involving clathrin as other types of endocytosis have not been demonstrated in yeast. 相似文献
8.
Bataille D Héron L Virsolvy A Peyrollier K LeCam A Gros L Blache P 《Cellular and molecular life sciences : CMLS》1999,56(1-2):78-84
ATP-dependent potassium (KATP) channels occupy a key position in the control of insulin release from the pancreatic β cell since they couple cell polarity
to metabolism. These channels close when more ATP is produced via glucose metabolism. They are also controlled by sulfonylureas,
a class of drugs used in type 2 diabetic patients for triggering insulin secretion from β cells that have lost part of their
sensitivity to glucose. We have demonstrated the existence of endogenous counterparts to sulfonylureas which we have called
‘endosulfines.’ In this review, we describe the discovery, isolation, cloning, and biological features of the high-molecular-mass
form, α-endosulfine, and discuss its possible role in the physiology of the β cell as well as in pathology.
Received 1 February 1999; received after revision 26 March 1999; accepted 26 March 1999 相似文献
9.
Synaptic target recognition is a complex molecular event. In a differentiating presynaptic terminal, relatively ‘rare’ molecules
first detect the cell identity of the synaptic target. Subsequently, many ‘common’ molecules continue the process of synaptogenesis.
We present a theoretical framework for understanding synaptic target recognition and discuss the features of its molecular
components and their integration, drawing on the rapid progress made in recent studies. 相似文献
10.
Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain 总被引:1,自引:0,他引:1
Rivera-Milla E Stuermer CA Málaga-Trillo E 《Cellular and molecular life sciences : CMLS》2006,63(3):343-357
Reggies (flotillins) are detergent-resistant microdomains involved in the scaffolding of large heteromeric complexes that
signal across the plasma membrane. Based on the presence of an evolutionarily widespread motif, reggies/flotillins have been
included within the SPFH (stomatin-prohibitin-flotillin-HflC/K) protein superfamily. To better understand the origin and evolution
of reggie/flotillin structure and function, we searched databases for reggie/flotillin and SPFH-like proteins in organisms
at the base and beyond the animal kingdom, and used the resulting dataset to compare their structural and functional domains.
Our analysis shows that the SPFH grouping has little phylogenetic support, probably due to convergent evolution of its members.
We also find that reggie/flotillin homologues are highly conserved among metazoans but are absent in plants, fungi and bacteria,
where only proteins with ‘reggie-like’ domains can be found. However, despite their low sequence similarities, reggie/flotillin
and ‘reggie-like’ domains appear to subserve related functions, suggesting that their basic biological role was acquired independently
during evolution.
Received 21 September 2005; received after revision 14 November 2005; accepted 21 November 2005 相似文献
11.
SNAREs and SNARE regulators in membrane fusion and exocytosis 总被引:21,自引:0,他引:21
J. E. Gerst 《Cellular and molecular life sciences : CMLS》1999,55(5):707-734
Eukaryotes have a remarkably well-conserved apparatus for the trafficking of proteins between intracellular compartments
and delivery to their target organelles. This apparatus comprises the secretory (or ‘protein export’) pathway, which is responsible
for the proper processing and delivery of proteins and lipids, and is essential for the derivation and maintenance of those
organelles. Protein transport between intracellular compartments is mediated by carrier vesicles that bud from one organelle
and fuse selectively with another. Therefore, organelle-specific trafficking of vesicles requires specialized proteins that
regulate vesicle transport, docking and fusion. These proteins are generically termed SNAREs and comprise evolutionarily conserved
families of membrane-associated proteins (i.e. the synaptobrevin/VAMP, syntaxin and SNAP-25 families) which mediate membrane
fusion. SNAREs act at all levels of the secretory pathway, but individual family members tend to be compartment-specific and,
thus, are thought to contribute to the specificity of docking and fusion events. In this review, we describe the different
SNARE families which function in exocytosis, as well as discuss the role of possible negative regulators (e.g. ‘SNARE-masters’)
in mediating events leading to membrane fusion. A model to illustrate the dynamic cycling of SNAREs between fusion-incompetent
and fusion-competent states, called the SNARE cycle, is presented.
Received 8 October 1998; received after revision 26 November 1998; accepted 26 November 1998 相似文献
12.
P. E. Pilet 《Cellular and molecular life sciences : CMLS》1998,54(8):851-865
Several characteristics of the plant hormone abscisic acid (ABA) are critically discussed, more or less directly, in relation
to the extension of root cells. A few topics have been selected some biochemical characteristics of ABA (chemical structure,
metabolism), inhibiting-β complex, inhibiting regulators from root caps, endogenous ABA in growing roots (ABA gradients, microsurgical experiments,
light effects), applied ABA on elongating roots, ABA and indol-3yl acetic acid (IAA) interactions (root growth, proton extrusion,
hormone transport, auxin herbicides), ABA effect on the root cell cycle, ABA and drought cells of elongating roots [water
deficit conditions, IAA and jasmonic acid (JA) as ‘stress hormones’ other than ABA, gene expression].
Received 28 January 1998; received after revision 20 April 1998; accepted 21 April 1998 相似文献
13.
Summary The presence of a glycolytic complex or particle has been demonstrated in the insect midgut form ofTrypanosoma brucei brucei. It differs from the ‘glycosome’ of the bloodstream form of the parasite in that 3-phosphoglycerate kinase is absent. The
latter enzyme appears to be cytosolic.
Acknowledgment. We are grateful to Dr R. Brun for the kind supply of the strain. The work was funded by the Swiss National
Science Foundation No. 3.331.0.78. 相似文献
14.
Insulin secretion is finely tuned to the requirements of tissues by tight coupling to prevailing blood glucose levels. The
normal regulation of insulin secretion is coupled to glucose metabolism in the pancreatic B cell, a major but not exclusive
signal for secretion being closure of K+ATP (adenosine triphosphate)-dependent channels in the cell membrane through an increase in cytosolic ATP/adenosine diphosphate.
Insulin secretion in type 2 diabetes is abnormal in several respects due to genetic causes but also due to the metabolic environment
of the pancreatic B cells. This environment may be particularly important for the deterioration of insulin secretion which
occurs with increasing duration of diabetes. Factors in the environment with potential importance include overstimulation,
a negative effect of hyperglycemia per se (‘glucotoxicity’) as well as adverse effects of elevated fatty acids (‘lipotoxicity’).
Elucidating the mechanisms behind these factors as well as their clinical importance will pave the way for treatment which
could preserve B-cell function in type 2 diabetic patients.
Received 4 October 1999; received after revision 1 November 1999; accepted 3 December 1999 相似文献
15.
M. L. Rose 《Cellular and molecular life sciences : CMLS》1998,54(9):965-978
The immunological properties of human endothelial cells suggest they perform a pivotal role in acute and chronic rejection
following solid organ transplantation. In this review the basic features of acute and chronic rejection are described as are
the cellular and molecular requirements for antigen presentation. Traditionally, antigen-presenting cells are considered to
be bone marrow-derived cells. However, these conclusions have been derived from rodent models of allograft rejection where
bone marrow-derived passenger leukocytes are the only source of donor major histocompatibility complex (MHC) class II in the
grafted organ. In contrast, in humans, virtually all the microvascular and small vessel endothelial cells are ‘constitutively’
positive for MHC class II antigens. The phenotypic properties of human endothelial cells, their response to cytokines and
their ability to stimulate resting T cells are described. Unlike bone marrow-derived antigen presenting cells (APCs), which
utilise B7/CD28 interactions, human endothelial cells utilise lymphocyte function antigen 3 (LFA3)/CD2 pathways to stimulate
T cells. They activate a CD45RO + B7-independent subpopulation of T cells. Their effect on allogeneic T cells is compared
with other non-bone marrow-derived cells such as fibroblasts, epithelial cells and smooth muscle cells, which are unable to
stimulate resting T cells. Evidence is presented suggesting that release of MHC and non-human leukocyte antigens (HLA) from
endothelial cells stimulates an alloantibody and autoimmune response leading to chronic rejection.
Received 30 March 1998; received after revision 4 May 1998; accepted 4 May 1998 相似文献
16.
Crabtree JW 《Cellular and molecular life sciences : CMLS》1999,56(7-8):683-700
The thalamus and cerebral cortex are linked together to form a vast network of interconnections. Different modes of interactions
among the cells in this network underlie different states of consciousness, such as wakefulness and sleep. Interposed between
the dorsal thalamus and cortex are the GABAergic neurons of the thalamic reticular nucleus (TRN), which play a pivotal role
not only in switching between the awake and sleep states but also in sensory processing during the awake state. The visual,
somatosensory, and auditory sectors of TRN share many of the same organizational features. Each of these sectors contains
maps, which are related to its inputs and outputs, and organizational components called ‘slabs.’ It is proposed that, during
wakefulness, TRN is crucially involved in resetting the activity levels in sensory nuclei of the dorsal thalamus, which allows
the cortex to actively and periodically compare its on-going sensory processing with the available sensory information.
Received 11 May 1999; received after revision 15 July 1999; accepted 21 July 1999 相似文献
17.
Pili in Gram-negative and Gram-positive bacteria — structure, assembly and their role in disease 总被引:2,自引:0,他引:2
Many bacterial species possess long filamentous structures known as pili or fimbriae extending from their surfaces. Despite
the diversity in pilus structure and biogenesis, pili in Gram-negative bacteria are typically formed by non-covalent homopolymerization
of major pilus subunit proteins (pilins), which generates the pilus shaft. Additional pilins may be added to the fiber and
often function as host cell adhesins. Some pili are also involved in biofilm formation, phage transduction, DNA uptake and
a special form of bacterial cell movement, known as ‘twitching motility’ In contrast, the more recently discovered pili in
Gram-positive bacteria are formed by covalent polymerization of pilin subunits in a process that requires a dedicated sortase
enzyme. Minor pilins are added to the fiber and play a major role in host cell colonization.
This review gives an overview of the structure, assembly and function of the best-characterized pili of both Gram-negative
and Gram-positive bacteria.
Received 08 August 2008; received after revision 24 September 2008; accepted 01 October 2008 相似文献
18.
ROPs in the spotlight of plant signal transduction 总被引:7,自引:0,他引:7
Berken A 《Cellular and molecular life sciences : CMLS》2006,63(21):2446-2459
Small guanine nucleotide binding proteins of the Rho family called ROP play a crucial role as regulators of signal transduction
in plants. They participate in pathways that influence growth and development, and the adaptation of plants to various environmental
situations. As members of the Ras superfamily, ROPs function as molecular switches cycling between a GDP-bound ‘off’ and a
GTP-bound ‘on’ state in a strictly regulated manner. Latest research provided fascinating new insights into ROP regulation
by novel guanine nucleotide exchange factors, unconventional GTPase activating proteins, and guanine nucleotide dissociation
inhibitors, which apparently organize localized ROP activation. Important progress has also been made concerning signaling
components upstream and downstream of the ROP cycle involving receptor-like serine/threonine kinases and effectors that can
manipulate cytoskeletal dynamics, intracellular calcium levels, H2O2 production and further cellular targets. This review outlines the fast developing knowledge on ROP GTPases highlighting their
specific features, regulation and roles in a cellular signaling context.
Received 28 April 2006; received after revision 2 June 2006; accepted 29 June 2006 相似文献
19.
Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A ‘recommended’
human diet contains significant quantities of polyphenolics, as they have long been assumed to be ‘antioxidants’ that scavenge
excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also
have ‘indirect’ antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence
for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive
or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last
2 – 3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and
metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects
and regulatory effects on energy metabolism and gut health.
Received 14 May 2007; received after revision 27 June 2007; accepted 24 July 2007 相似文献
20.
Sergio Porté Agrin Moeini Irene Reche Naeem Shafqat Udo Oppermann Jaume Farrés Xavier Parés 《Cellular and molecular life sciences : CMLS》2011,68(6):1065-1077
Human ζ-crystallin is a Zn2+-lacking medium-chain dehydrogenase/reductase (MDR) included in the quinone oxidoreductase (QOR) family because of its activity
with quinones. In the present work a novel enzymatic activity was characterized: the double bond α,β-hydrogenation of medium-chain
2-alkenals and 3-alkenones. The enzyme is especially active with lipid peroxidation products such as 4-hydroxyhexenal, and
a role in their detoxification is discussed. This specificity is novel in the QOR family, and it is similar to that described
in the distantly related alkenal/one reductase family. Moreover, we report the X-ray structure of ζ-crystallin, which represents
the first structure solved for a tetrameric Zn2+-lacking MDR, and which allowed the identification of the active-site lining residues. Docking simulations suggest a role
for Tyr53 and Tyr59 in catalysis. The kinetics of Tyr53Phe and Tyr59Phe mutants support the implication of Tyr53 in binding/catalysis
of alkenal/one substrates, while Tyr59 is involved in the recognition of 4-OH-alkenals. 相似文献