共查询到20条相似文献,搜索用时 468 毫秒
1.
Sudhir Kumar Singh Himanshu Pandey Jawdat Al-Bassam Larisa Gheber 《Cellular and molecular life sciences : CMLS》2018,75(10):1757-1771
Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942–4954, 2011; Roostalu et al., Science 332:94–99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs. 相似文献
2.
Myosin V from head to tail 总被引:1,自引:1,他引:0
Trybus KM 《Cellular and molecular life sciences : CMLS》2008,65(9):1378-1389
Myosin V (myoV), a processive cargo transporter, has arguably been the most well-studied unconventional myosin of the past
decade. Considerable structural information is available for the motor domain, the IQ motifs with bound calmodulin or light
chains, and the cargo-binding globular tail, all of which have been crystallized. The repertoire of adapter proteins that
link myoV to a particular cargo is becoming better understood, enabling cellular transport processes to be dissected. MyoV
is processive, meaning that it takes many steps on actin filaments without dissociating. Its extended lever arm results in
long 36-nm steps, making it ideal for single molecule studies of processive movement. In addition, electron microscopy revealed
the structure of the inactive, folded conformation of myoV when it is not transporting cargo. This review provides a background
on myoV, and highlights recent discoveries that show why myoV will continue to be an active focus of investigation.
Received 31 October 2007; received after revision 4 December 2007; accepted 2 January 2008 相似文献
3.
Llorca O 《Cellular and molecular life sciences : CMLS》2008,65(9):1302-1310
In mammals, the mannose receptor family consists of four members, Endo180, DEC-205, phospholipase A2 receptor and the mannose receptor. The extracellular domains of all these receptors contain a similar arrangement of domains
in which an Nterminal cysteine-rich domain is followed by a single fibronectin type II domain and eight or ten C-type lectin-like
domains. This review focuses on the threedimensional structure of the receptors in the mannose receptor family and its functional
implication. Recent research has revealed that several members of this family can exist in at least two configurations: an
extended conformation with the N-terminal cysteinerich domain pointing outwards from the cell membrane and a bent conformation
where the N-terminal domains fold back to interact with C-type lectin-like domains at the middle of the structure. Conformational
transitions between these two states seem to regulate the interaction of these receptors with ligands and their oligomerization.
Received 25 October 2007; received after revision 23 November 2007; accepted 7 December 2007 相似文献
4.
Images, calculated from electron micrographs, show the three-dimensional structures of microtubules and tubulin sheets decorated stoichiometrically with motor protein molecules. Dimeric motor domains (heads) of kinesin and ncd, the kinesin-related protein that moves in the reverse direction, each appeared to bind to tubulin in the same way, by one of their two heads. The second heads show an interesting difference in position that seems to be related to the directions of movement of the two motors. X-ray crystallographic results showing the structures of kinesin and ncd to be very similar at atomic resolution, and homologous also to myosin, suggest that the two motor families may use mechanisms that have much in common. Nevertheless, myosins and kinesins differ kinetically. Also, whereas conformational changes in the myosin catalytic domain are amplified by a long lever arm that connects it to the stalk domain, kinesin and ncd do not appear to possess a structure with a similar function but may rely on biased diffusion in order to move along microtubules. 相似文献
5.
The structural and functional analysis of biological macromolecules has reached a level of resolution that allows mechanistic interpretations of molecular action, giving rise to the view of enzymes as molecular machines. This machine analogy is not merely metaphorical, as bio-analogous molecular machines actually are being used as motors in the fields of nanotechnology and robotics. As the borderline between molecular cell biology and technology blurs, developments in the engineering and material sciences become increasingly instructive sources of models and concepts for biologists. In this review, we provide a--necessarily selective--summary of recent progress in the usage of biological and biomimetic materials as actuators in artificial environments, focussing on motors built from DNA, classical cellular motor systems (tubulin/kinesin, actin/myosin), the rotary motor F1F0-ATPase and protein-based 'smart' materials. 相似文献
6.
Tatyana A. Sysoeva 《Cellular and molecular life sciences : CMLS》2017,74(6):1001-1018
ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors. 相似文献
7.
The BAG (Bcl-2 associated athanogene) family is a multifunctional group of proteins that perform diverse functions ranging from apoptosis to tumorigenesis.
An evolutionarily conserved group, these proteins are distinguished by a common conserved region known as the BAG domain.
BAG genes have been found in yeasts, plants, and animals, and are believed to function as adapter proteins forming complexes
with signaling molecules and molecular chaperones. In humans, a role for BAG proteins has been suggested in carcinogenesis,
HIV infection, and Parkinson’s disease. These proteins are therefore potential therapeutic targets, and their expression in
cells may serve as a predictive tool for such diseases. In plants, the Arabidopsis thaliana genome contains seven homologs of the BAG family, including four with domain organization similar to animal BAGs. Three members
contain a calmodulin-binding domain possibly reflecting differences between plant and animal programmed cell death. This review
summarizes current understanding of BAG proteins in both animals and plants.
Received 21 November 2007; received after revision 17 December 2007; accepted 2 January 2008 相似文献
8.
Cole DG 《Cellular and molecular life sciences : CMLS》1999,56(3-4):217-226
The kinesins constitute a large family of motor proteins which are responsible for the distribution of numerous organelles, vesicles and macromolecular complexes throughout the cell. One class of these molecular motors, kinesin-II, is unique in that these proteins are typically found as heterotrimeric complexes containing two different, though related, kinesin-like motor subunits, and a single nonmotor subunit. The heteromeric nature of these kinesins appears to have resulted in a class of combinatorial kinesins which can 'mix and match' different motor subunits. Another novel feature of these motors is that the activities of several kinesin-II representatives are essential in the assembly of motile and nonmotile cilia, a role not attributed to any other kinesin. This review presents a brief overview of the structure and biological functions of kinesin-II, the heteromeric kinesin. 相似文献
9.
Hiroshi Ueno Kano Suzuki Takeshi Murata 《Cellular and molecular life sciences : CMLS》2018,75(10):1789-1802
Rotary ATPases are unique rotary molecular motors that function as energy conversion machines. Among all known rotary ATPases, F1-ATPase is the best characterized rotary molecular motor. There are many high-resolution crystal structures and the rotation dynamics have been investigated in detail by extensive single-molecule studies. In contrast, knowledge on the structure and rotation dynamics of V1-ATPase, another rotary ATPase, has been limited. However, recent high-resolution structural studies and single-molecule studies on V1-ATPase have provided new insights on how the catalytic sites in this molecular motor change its conformation during rotation driven by ATP hydrolysis. In this review, we summarize recent information on the structural features and rotary dynamics of V1-ATPase revealed from structural and single-molecule approaches and discuss the possible chemomechanical coupling scheme of V1-ATPase with a focus on differences between rotary molecular motors. 相似文献
10.
The RecQ helicases belong to the Superfamily II group of DNA helicases, and are defined by amino acid motifs that show sequence
similarity to the catalytic domain of Escherichia coli RecQ. RecQ helicases have crucial roles in the maintenance of genome stability. In humans, there are five RecQ helicases
and deficiencies in three of them cause genetic disorders characterised by cancer predisposition, premature aging and/or developmental
abnormalities. RecQ helicase-deficient cells exhibit aberrant genetic recombination and/or DNA replication, which result in
chromosomal instability and a decreased potential for proliferation. Here, we review the current knowledge of the molecular
genetics of RecQ helicases, focusing on the human RecQ helicase disorders and mouse models of these conditions.
Received 9 March 2007; received after revision 26 April 2007; accepted 2 May 2007 相似文献
11.
Ruminations on dietary restriction and aging 总被引:6,自引:0,他引:6
Kennedy BK Steffen KK Kaeberlein M 《Cellular and molecular life sciences : CMLS》2007,64(11):1323-1328
Calorie restriction has been known for many decades to extend the life span of rodents. Since the more recent discovery that
a long-term reduction in nutrient intake also extends life span in nearly every invertebrate model organism used for aging
research, the mechanisms behind the longevity benefits of this intervention have been under intense scrutiny. While models
have been developed in yeast, worms, and flies, the molecular mechanisms governing life span extension by calorie restriction
remain controversial, resulting in great anticipation of mammalian studies testing these models. Here we discuss the links
between nutrient reduction and enhanced longevity with emphasis on evolutionarily conserved nutrient response signaling.
Received 1 November 2006; received after revision 15 December 2006; accepted 27 February 2007 相似文献
12.
Both the development and the maintenance of neurons require a great deal of active cytoplasmic transport. Much of this transport is driven by microtubule motor proteins. Membranous organelles and other macromolecular assemblies bind motor proteins that then use cycles of adenosine 5'-triphosphate hydrolysis to move these 'cargoes' along microtubules. Different sets of cargoes are transported to distinct locations in the cell. The resulting differential distribution of materials almost certainly plays an important part in generating polarized neuronal morphologies and in maintaining their vectorial signalling activities. A number of different microtubule motor proteins function in neurons; presumably they are specialized for accomplishing different transport tasks. Questions about specific motor functions and the functional relationships between different motors present a great challenge. The answers will provide a much deeper understanding of fundamental transport mechanisms, as well as how these mechanisms are used to generate and sustain cellular asymmetries. 相似文献
13.
Samuel CS Hewitson TD Unemori EN Tang ML 《Cellular and molecular life sciences : CMLS》2007,64(12):1539-1557
The peptide hormone relaxin is emerging as a multi-functional factor in a broad range of target tissues including several
non-reproductive organs, in addition to its historical role as a hormone of pregnancy. This review discusses the evidence
that collectively demonstrates the many diverse and vital roles of relaxin: the homeostatic role of endogenous relaxin in
mammalian pregnancy and ageing; its gender-related effects; the therapeutic effects of relaxin in the treatment of fibrosis,
inflammation, cardioprotection, vasodilation and wound healing (angiogenesis) amongst other pathophysiological conditions,
and its potential mechanism of action. Furthermore, translational issues using experimental models (to humans) and its use
in various clinical trials, are described, each with important lessons for the design of future trials involving relaxin.
The diverse physiological and pathological roles for relaxin have led to the search for its significance in humans and highlight
its potential as a drug of the future.
Received 12 December 2006; received after revision 12 February 2007; accepted 15 March 2007 相似文献
14.
Rosenstiel P Jacobs G Till A Schreiber S 《Cellular and molecular life sciences : CMLS》2008,65(9):1361-1377
NOD-like receptors (NLRs) comprise a family of cytosolic proteins that have been implicated as ancient cellular sentinels
mediating protective immune responses elicited by intracellular pathogens or endogenous danger signals. Genetic variants in
NLR genes have been associated with complex chronic inflammatory barrier diseases (e.g. Crohn disease, bronchial asthma). In
this review, we focus on the molecular pathophysiology of NLRs in the context of chronic inflammatory diseases and pinpoint
recent advances in the evolutionary understanding of NLR biology. We propose that the field of NLRs may serve as a prototype
for how a comprehensive understanding of an element of the immunological barrier will eventually lead to the development of
targeted diagnostic, therapeutic and/or preventive strategies.
Received 29 October 2007; received after revision 10 December 2007; accepted 19 December 2007 相似文献
15.
Eosinophils are traditionally thought to form part of the innate immune response against parasitic helminths acting through
the release of cytotoxic granule proteins. However, they are also a central feature in asthma. From their development in the
bone marrow to their recruitment to the lung via chemokines and cytokines, they form an important component of the inflammatory
milieu observed in the asthmatic lung following allergen challenge. A wealth of studies has been performed in both patients
with asthma and in mouse models of allergic pulmonary inflammation to delineate the role of eosinophils in the allergic response.
Although the long-standing association between eosinophils and the induction of airway hyper-responsiveness remains controversial,
recent studies have shown that eosinophils may also promote airway remodelling. In addition, emerging evidence suggests that
the eosinophil may also serve to modulate the immune response. Here we review the highly co-ordinated nature of eosinophil
development and trafficking and the evolution of the eosinophil as a multi-factoral leukocyte with diverse functions in asthma.
Received 6 December 2006; received after revision 11 January 2007; accepted 15 February 2007 相似文献
16.
At the moment of insemination millions of mammalian sperm cells are released into the female reproductive tract in order to
find a single cell – the oocyte. The spermatozoa subsequently ignore the thousands of cells they make contact with during
their journey to the site of fertilisation, until they reach the surface of the oocyte. At this point, they bind tenaciously
to the acellular coat, known as the zona pellucida, that surrounds the oocyte and initiate the chain of cellular interactions
that will culminate in fertilization. These exquisitely cell- and species-specific recognition events are among the most strategically
important cellular interactions in biology. Understanding the cellular and molecular mechanisms that underpin them has implications
for diagnosis of the aetiology of human infertility and the development of novel targets for fertility regulation. Herein,
we describe two models indicating the plethora of highly orchestrated molecular interactions underlying successful sperm zona
binding and sperm oocyte fusion.
Received 17 December 2006; received after revision 31 January 2007; accepted 16 March 2007 相似文献
17.
Christian Schumacher 《Journal of forecasting》2007,26(4):271-302
This paper discusses the forecasting performance of alternative factor models based on a large panel of quarterly time series for the German economy. One model extracts factors by static principal components analysis; the second model is based on dynamic principal components obtained using frequency domain methods; the third model is based on subspace algorithms for state‐space models. Out‐of‐sample forecasts show that the forecast errors of the factor models are on average smaller than the errors of a simple autoregressive benchmark model. Among the factor models, the dynamic principal component model and the subspace factor model outperform the static factor model in most cases in terms of mean‐squared forecast error. However, the forecast performance depends crucially on the choice of appropriate information criteria for the auxiliary parameters of the models. In the case of misspecification, rankings of forecast performance can change severely. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
18.
Mitochondria are cellular organelles of crucial importance, playing roles in cellular life and death. In certain cell types, such as neurons, mitochondria must travel long distances so as to meet metabolic demands of the cell. Mitochondrial movement is essentially microtubule (MT) based and is executed by two main motor proteins, Dynein and Kinesin. The organization of the cellular MT network and the identity of motors dictate mitochondrial transport. Tight coupling between MTs, motors, and the mitochondria is needed for the organelle precise localization. Two adaptor proteins are involved directly in mitochondria-motor coupling, namely Milton known also as TRAK, which is the motor adaptor, and Miro, which is the mitochondrial protein. Here, we discuss the active mitochondria transport process, as well as motor–mitochondria coupling in the context of MT organization in different cell types. We focus on mitochondrial trafficking in different cell types, specifically neurons, migrating cells, and polarized epithelial cells. 相似文献
19.
Lonez C Legat A Vandenbranden M Ruysschaert JM 《Cellular and molecular life sciences : CMLS》2008,65(4):620-630
The inflammatory effect of unmethylated CpG DNA sequences represents a major obstacle to the use of cationic lipids for in vivo gene therapy. Although the mechanism of CpG-induced inflammatory response is rather well understood nowadays, few solutions
have been designed to circumvent this effect in gene therapy experiments. Our previous work has shown that a refractory state
towards inflammation can be elicited by preinjecting cationic liposomes. Here, we present evidence that diC14-amidine liposomes
confer new anti-inflammatory properties to phospholipids from low-density lipoprotein (LDL) and even to synthetic phospholipids
for which such an observation has not been reported so far. Whereas oxidation of LDL lipids was a prerequisite for any anti-inflammatory
activity, lipid oxidation is no longer required in our experiments, suggesting that cationic lipids transport phospholipids
through a different route and affect different pathways.This opens up new possibilities for manipulating inflammatory responses
in gene therapy protocols but also in a general manner in immunological experiments.
Received 12 November 2007; received after revision 4 December 2007; accepted 4 December 2007 相似文献
20.
Cajal bodies (CBs) and Gems are nuclear domains that contain factors responsible for spliceosomal small nuclear ribonucleoprotein
(snRNP) biogenesis. The marker protein for CBs is coilin. In addition to snRNPs, coilin and other factors, canonical CBs contain
the survivor of motor neuron protein (SMN). SMN can also localize to Gems. Considering the important role that coilin plays
in the formation and composition of CBs, we tested the splicing efficiency of several cell lines that vary in regards to coilin
level and modification using an artificial reporter substrate. We found that cells with both hypomethylated coilin and Gems
are more efficient at reporter splicing compared to cells in which SMN localizes to CBs. In contrast, coilin reduction, which
induces Gem formation, decreases cell proliferation and artificial reporter splicing. These findings demonstrate that coilin
modifications or levels impact artificial reporter splicing, possibly by influencing snRNP biogenesis.
Received 26 December 2007; received after revision 5 February 2008; accepted 7 February 2008 相似文献