共查询到20条相似文献,搜索用时 62 毫秒
1.
Wenbo Zhou Chunmei Long Anthony L. Fink Vladimir N. Uversky 《Central European Journal of Biology》2010,5(1):11-20
α-Synuclein, a natively unfolded protein aggregation which is implicated in the pathogenesis of Parkinson’s disease and several
other neurodegenerative diseases, is known to interact with a great number of unrelated proteins. Some of these proteins,
such as β-synuclein and DJ-1, were shown to inhibit α-synuclein aggregation in vitro and in vivo therefore acting as chaperones. Since calbindin-D28K is co-localized with Ca2+ neuronal membrane pumps, and since α-synuclein is also found in the membrane proximity, these two proteins can potentially
interact in vivo. Here we show that calbindin-D28K interacts with α-synuclein and inhibits its fibrillation in a calcium-dependent manner,
therefore potentially acting as a calcium-dependent chaperone. 相似文献
2.
Background
The polypeptides involved in amyloidogenesis may be globular proteins with a defined 3D-structure or natively unfolded proteins. The first class includes polypeptides such as β2-microglobulin, lysozyme, transthyretin or the prion protein, whereas β-amyloid peptide, amylin or α-synuclein all belong to the second class. Recent studies suggest that specific regions in the proteins act as "hot spots" driving aggregation. This should be especially relevant for natively unfolded proteins or unfolded states of globular proteins as they lack significant secondary and tertiary structure and specific intra-chain interactions that can mask these aggregation-prone regions. Prediction of such sequence stretches is important since they are potential therapeutic targets. 相似文献3.
4.
Du HN Li HT Zhang F Lin XJ Shi JH Shi YH Ji LN Hu J Lin DH Hu HY 《FEBS letters》2006,580(15):3657-3664
alpha-Synuclein (alpha-Syn), amyloid beta-protein and prion protein are among the amyloidogenic proteins that are associated with the neurodegenerative diseases. These three proteins share a homologous region with a consensus sequence mainly consisting of glycine, alanine and valine residues (accordingly named as the GAV motif), which was proposed to be the critical core for the fibrillization and cytotoxicity. To understand the role of the GAV motif in protein amyloidogenesis, we studied the effects of the homologous peptides corresponding to the sequence of GAV motif region (residues 66-74) on alpha-Syn aggregation. The result shows that these peptides can promote fibrillization of wild-type alpha-Syn and induce that of the charge-incorporated mutants but not the GAV-deficient alpha-Syn mutant. The acceleration of alpha-Syn aggregation by the homologous peptides is under a sequence-specific manner. The interplay between the GAV peptide and the core regions in alpha-Syn may accelerate the aggregation process and stabilize the fibrils. This finding provides clues for developing peptide mimics that could promote transforming the toxic oligomers or protofibrils into the inert mature fibrils. 相似文献
5.
Subunit 3 (Rpb3) of eukaryotic RNA polymerase II is a homologue of the α subunit of prokaryotic RNA polymerase, which plays
a key role in subunit assembly of this complex enzyme by providing the contact surfaces for both β and β′ subunits. Previously
we demonstrated that the Schizosaccharomyces pombe Rpb3 protein forms a core subassembly together with Rpb2 (the β homologue) and Rpb11 (the second α homologue) subunits, as
in the case of the prokaryotic α2β complex. In order to obtain further insight into the physiological role(s) of Rpb3, we subjected the S. pombe rpb3 gene to mutagenesis. A total of nine temperature-sensitive (Ts) and three cold-sensitive (Cs) S. pombe mutants have been isolated, each (with the exception of one double mutant) carrying a single mutation in the rpb3 gene in one of the four regions (A–D) that are conserved between the homologues of eukaryotic subunit 3. The three Cs mutations
were all located in region A, in agreement with the central role of the corresponding region in the assembly of prokaryotic
RNA polymerase; the Ts mutations, in contrast, were found in all four regions. Growth of the Ts mutants was reduced to various
extents at non-permissive temperatures. Since the metabolic stability of most Ts mutant Rpb3 proteins was markedly reduced
at non-permissive temperature, we predict that these mutant Rpb3 proteins are defective in polymerase assembly or the mutant
RNA polymerases containing mutant Rpb3 subunits are unstable. In accordance with this prediction, the Ts phenotype of all
the mutants was suppressed to varying extents by over-expression of Rpb11, the pairing partner of Rpb3 in the core subassembly.
We conclude that the majority of rpb3 mutations affect the assembly of Rpb3, even though their effects on subunit assembly vary depending on the location of the
mutation considered.
Received: 25 January 1999 / Accepted: 27 April 1999 相似文献
6.
The conversion from α-helix to β-strand that has been widely observed in so-called chameleon sequences has received considerable attention since such a structural change may induce many amyloidogenic proteins to self-assemble into fibrils thus causing fatal diseases. Here we report a large scale-analysis of the energetics of secondary structural conversions in a collection of chameleon sequences retrieved from the Protein Data Bank. Major energetic contributions to the secondary structural conversion were analyzed by carrying out energy decomposition on a pairwise per-residue basis, i.e., (i,i), (i,i ± 1), (i,i ± 2), (i,i ± 3), (i,i ± 4) and > (i,i ± 4) intra-/inter-residual interactions. While the overall potential energy differences were subtle, individual residue-based interacting energy differences were observed to vary significantly depending on the specific type of secondary structural conversion. The average energy difference between α-helix and β-strand, <ΔE
α→β>, in the chameleon sequences varied significantly in (i,i), (i,i ± 1) and > (i,i ± 4) interactions. The major energetic factors in secondary structure conversions were electrostatic interactions and the polar term for solvation energy. In addition, residue-based average energy differences in α-helix → β-strand conversions were well-correlated to those in α-helix → random coil → β-strand conversions (R
2 = 0.92). Assuming that three secondary structural elements can transform in either direction, this strong correlation indicates that the present energy decomposition method using database structures of chameleon sequences provides a reliable tool for the characterization of secondary structure fluctuations in amino acid sequences. 相似文献
7.
8.
Sanne M. Nabuurs Bregje J. de Kort Adrie H. Westphal Carlo P. M. van Mierlo 《European biophysics journal : EBJ》2010,39(4):689-698
Transient structures in unfolded proteins are important in elucidating the molecular details of initiation of protein folding.
Recently, native and non-native secondary structure have been discovered in unfolded A. vinelandii flavodoxin. These structured elements transiently interact and subsequently form the ordered core of an off-pathway folding
intermediate, which is extensively formed during folding of this α–β parallel protein. Here, site-directed spin-labelling
and paramagnetic relaxation enhancement are used to investigate long-range interactions in unfolded apoflavodoxin. For this
purpose, glutamine-48, which resides in a non-native α-helix of unfolded apoflavodoxin, is replaced by cysteine. This replacement
enables covalent attachment of nitroxide spin-labels MTSL and CMTSL. Substitution of Gln-48 by Cys-48 destabilises native
apoflavodoxin and reduces flexibility of the ordered regions in unfolded apoflavodoxin in 3.4 M GuHCl, because of increased hydrophobic interactions in the unfolded protein. Here, we report that in the study of the conformational
and dynamic properties of unfolded proteins interpretation of spin-label data can be complicated. The covalently attached
spin-label to Cys-48 (or Cys-69 of wild-type apoflavodoxin) perturbs the unfolded protein, because hydrophobic interactions
occur between the label and hydrophobic patches of unfolded apoflavodoxin. Concomitant hydrophobic free energy changes of
the unfolded protein (and possibly of the off-pathway intermediate) reduce the stability of native spin-labelled protein against
unfolding. In addition, attachment of MTSL or CMTSL to Cys-48 induces the presence of distinct states in unfolded apoflavodoxin.
Despite these difficulties, the spin-label data obtained here show that non-native contacts exist between transiently ordered
structured elements in unfolded apoflavodoxin. 相似文献
9.
Aisenbrey C Borowik T Byström R Bokvist M Lindström F Misiak H Sani MA Gröbner G 《European biophysics journal : EBJ》2008,37(3):247-255
The fate of proteins with amyloidogenic properties depends critically on their immediate biochemical environment. However,
the role of biological interfaces such as membrane surfaces, as promoters of pathological aggregation of amyloidogenic proteins,
is rarely studied and only established for the amyloid-β protein (Aβ) involved in Alzheimer’s disease, and α-synuclein in
Parkinsonism. The occurrence of binding and misfolding of these proteins on membrane surfaces, is poorly understood, not at
least due to the two-dimensional character of this event. Clearly, the nature of the folding pathway for Aβ protein adsorbed
upon two-dimensional aggregation templates, must be fundamentally different from the three-dimensional situation in solution.
Here, we summarize the current research and focus on the function of membrane interfaces as aggregation templates for amyloidogenic
proteins (and even prionic ones). One major aspect will be the relationship between membrane properties and protein association
and the consequences for amyloidogenic products. The other focus will be on a general understanding of protein folding pathways
on two-dimensional templates on a molecular level. Finally, we will demonstrate the potential importance of membrane-mediated
aggregation for non-amphiphatic soluble amyloidogenic proteins, by using the SOD1 protein involved in the amyotrophic lateral
sclerosis syndrome.
Australian Society for Biophysics Special Issue: Metals and Membranes in Neuroscience. 相似文献
10.
The amino acid sequences of 22 α-amylases from family 13 of glycosyl hydrolases were analyzed with the aim of revealing the
evolutionary relationships between the archaeal α-amylases and their eubacterial and eukaryotic counterparts. Two evolutionary
distance trees were constructed: (i) the first one based on the alignment of extracted best-conserved sequence regions (58
residues) comprising β2, β3, β4, β5, β7, and β8 strand segments of the catalytic (α/β)8-barrel and a short conserved stretch in domain B protruding out of the barrel in the β3 →α3 loop, and (ii) the second one
based on the alignment of the substantial continuous part of the (α/β)8-barrel involving the entire domain B (consensus length: 386 residues). With regard to archaeal α-amylases, both trees compared
brought, in fact, the same results; i.e., all family 13 α-amylases from domain Archaea were clustered with barley pI isozymes,
which represent all plant α-amylases. The enzymes from Bacillus licheniformis and Escherichia coli, representing liquefying and cytoplasmic α-amylases, respectively, seem to be the further closest relatives to archaeal α-amylases.
This evolutionary relatedness clearly reflects the discussed similarities in the amino acid sequences of these α-amylases,
especially in the best-conserved sequence regions. Since the results for α-amylases belonging to all three domains (Eucarya,
Eubacteria, Archaea) offered by both evolutionary trees are very similar, it is proposed that the investigated conserved sequence
regions may indeed constitute the ``sequence fingerprints' of a given α-amylase.
Received: 3 June 1998 / Accepted: 20 August 1998 相似文献
11.
Beyer K 《Cell biochemistry and biophysics》2007,47(2):285-299
A key feature in Parkinson’s disease is the deposition of Lewy bodies. The major protein component of these intracellular
deposits is the 140-amino acid protein α-synuclein that is widely distributed throughout the brain. α-synuclein was identified
in presynaptic terminals and in synaptosomal preparations. The protein is remarkable for its structural variability. It is
almost unstructured as a monomer in aqueous solution. Self-aggregation leads to a variety of β-structures, while membrane
association may result in the formation of an amphipathic helical structure. The present article strives to give an overview
of what is currently known on the interaction of α-synuclein with lipid membranes, including synthetic lipid bilayers, membraneous
cell fractions, synaptic vesicles and intact cells. Manifestations of a functional relevance of the α-synuclein–lipid interaction
will be discussed and the potential pathogenicity of oligomeric α-synuclein aggregates will be briefly reviewed. 相似文献
12.
13.
Tatsuji Sakamoto Yuya Tsujitani Keiko Fukamachi Yuya Taniguchi Hideshi Ihara 《Applied microbiology and biotechnology》2010,86(4):1115-1124
Two distinct extracellular bifunctional proteins with β-L-arabinopyranosidase/α-D-galactopyranosidase activities were purified
from the culture filtrate of Fusarium oxysporum 12S. The molecular masses of the enzymes were estimated to be 55 (Fo/AP1) and 73 kDa (Fo/AP2) by SDS-PAGE. They hydrolyzed
both p-nitrophenyl β-L-arabinopyranoside and p-nitrophenyl α-D-galactopyranoside with different specificities. Fo/AP1 also showed low activity towards α-D-galactopyranosyl
oligosaccharides such as raffinose. Interestingly, both enzymes hydrolyzed larch wood arabinogalactan (releasing arabinose)
but not carob galactomannan, which has α-D-galactopyranosyl side chains. When larch wood arabinogalactan was incubated with
excess Fo/AP1 or Fo/AP2, both enzymes released approximately 10% of the total arabinose in the substrate. cDNAs encoding Fo/AP1
and Fo/AP2 (Foap1 and Foap2) were isolated by in vitro cloning. The coding sequences of Foap1 and Foap2 genes were 1,647 and 1,620 bp in length and encode polypeptides of 549 and 540 amino acids, respectively. The N-terminal
halves of both proteins had high similarity to putative conserved domains of the melibiase superfamily (Pfam account number
02065). The deduced amino acid sequences of the two enzymes indicate that they belong to glycosyl hydrolase family 27. Moreover,
the C-terminal regions of both proteins contain a putative family 35 carbohydrate-binding module. 相似文献
14.
Seven analogues of p-nitrophenyl T-antigen [Galβ(1→3)GalNAcα(1→O)PNP] have been synthesized as potential substrates for elucidation of the substrate specificity of endo-α-N-acetylgalactosaminidase. These compounds, which are commercially unavailable, include: GlcNAcβ(1→3){GlcNAcβ(1→6)}GalNAcα(1→O)PNP [core 4 type], GalNAcα(1→3)GalNAcα(1→O)PNP [core 5 type], GlcNAcβ(1→6)GalNAcα(1→O)PNP [core 6 type], GalNAcα(1→6)GalNAcα(1→O)PNP [core 7 type], Galα(1→3)GalNAcα(1→O)PNP [core 8 type], Glcβ(1→3)GalNAcα(1→O)PNP and GalNAcβ(1→3)GalNAcα(1→O)PNP. The assembly of these synthetic probes was accomplished efficiently, based on di-tert-butylsilylene(DTBS)-directed α-galactosylation as a key reaction. 相似文献
15.
Eslami G Frikha F Salehi R Khamesipour A Hejazi H Nilforoushzadeh MA 《Molecular biology reports》2011,38(6):3765-3776
Leishmania, a digenetic protozoan parasite causes severe diseases in human and animals. Efficient evasion of toxic microbicidal molecules,
such as reactive oxygen species and reactive nitrogen species is crucial for Leishmania to survive and replicate in the host cells. Tryparedoxin peroxidase, a member of peroxiredoxins family, is vital for parasite
survival in the presence of antioxidant, hence it is one of the most important molecules in Leishmania viability and then, it may be an appropriate goal for challenging against leishmaniasis. After cloning and sub-cloning of
TRYP6 from Leishmania major (MRHO/IR/75/ER), homology modeling of the LmTRYP6 was proposed to predict some functional property of this protein. The refined model showed that the core structure consists
of a seven β stranded β-sheet and five α helices which are organized as a central 7-stranded β2-β1-β5-β4-β3-β6-β7 surrounded
by 2-stranded β-hairpin, α helices A and D on one side, and α helices B, C and E on the other side. The peroxidatic active
site is located in a pocket formed by the residue Pro45, Met46, Thr49, Val51, Cys52, Arg128, Met147 and Pro 148. The catalytic
Cys52, located in the first turn of helix αB, is in van der Waals with a Pro45, a Thr49 and an Arg128 that are absolutely
conserved in all known Prx sequences. In this study, an attractive molecular target was studied. These results might be used
in designing of drugs to fight an important human pathogen. 相似文献
16.
The chloroplast ATP synthase (ATPase) utilizes the energy of a transmembrane electrochemical proton gradient to drive the
synthesis of ATP from ADP and phosphate. The chloroplast ATPase α and β subunits are the essential components of multisubunit protein complex. In this paper, the full-length cDNA and genomic DNA
of ATPase α (designated as GbatpA) and β (designated as GbatpB) subunit genes were isolated from Ginkgo biloba. The GbatpA and GbatpB genes were both intronless. The coding regions of GbatpA and GbatpB were 1530 bp and 1497 bp long, respectively, and their deduced amino acid sequences showed high degrees of identity to those
of other plant ATPase α and β proteins, respectively. The expression analysis by RT-PCR revealed that GbatpA and GbatpB both expressed in tissue-specific manners in G. biloba and might involve in leaf development. The recombinant GbATPB protein was successfully expressed in E. coli strain using pET28a vector with ATPase activity as three times high as the control, and the results showed that the molecular
weight of the recombinant protein was about 54 kDa, a size that was in agreement with that predicted by bioinformatics analysis.
This study provides useful information for further studying on overall structure, function and regulation of the chloroplast
ATPase in G. biloba, the so-called “living fossil” plant as one of the oldest gymnosperm species.
These authors contributed equally to this work 相似文献
17.
The available amino acid sequences of the α-amylase family (glycosyl hydrolase family 13) were searched to identify their
domain B, a distinct domain that protrudes from the regular catalytic (β/α)8-barrel between the strand β3 and the helix α3. The isolated domain B sequences were inspected visually and also analyzed
by Hydrophobic Cluster Analysis (HCA) to find common features. Sequence analyses and inspection of the few available three-dimensional
structures suggest that the secondary structure of domain B varies with the enzyme specificity. Domain B in these different
forms, however, may still have evolved from a common ancestor. The largest number of different specificities was found in
the group with structural similarity to domain B from Bacillus cereus oligo-1,6-glucosidase that contains an α-helix succeeded by a three-stranded antiparallel β-sheet. These enzymes are α-glucosidase,
cyclomaltodextrinase, dextran glucosidase, trehalose-6-phosphate hydrolase, neopullulanase, and a few α-amylases. Domain B
of this type was observed also in some mammalian proteins involved in the transport of amino acids. These proteins show remarkable
similarity with (β/α)8-barrel elements throughout the entire sequence of enzymes from the oligo-1,6-glucosidase group. The transport proteins, in
turn, resemble the animal 4F2 heavy-chain cell surface antigens, for which the sequences either lack domain B or contain only
parts thereof. The similarities are compiled to indicate a possible route of domain evolution in the α-amylase family.
Received: 4 December 1996 / Accepted: 13 March 1997 相似文献
18.
Andrew MF Liu Rico KH Lo Emily X Guo Maurice KC Ho Richard D Ye Yung H Wong 《BMC structural biology》2011,11(1):17
Background
G protein-coupled receptors constitute the largest family of cell surface receptors in the mammalian genome. As the core of the G protein signal transduction machinery, the Gα subunits are required to interact with multiple partners. The GTP-bound active state of many Gα subunits can bind a multitude of effectors and regulatory proteins. Yet it remains unclear if the different proteins utilize distinct or common structural motifs on the Gα subunit for binding. Using Gα16 as a model, we asked if its recently discovered adaptor protein tetratricopeptide repeat 1 (TPR1) binds to the same region as its canonical effector, phospholipase Cβ (PLCβ). 相似文献19.
Kikuchi T 《Amino acids》2008,35(3):541-549
It is well-known that the IgG-binding domain from staphylococcal protein A folds into a 3α helix bundle structure, while the
IgG-binding domain of streptococcal protein G forms an (α + β) structure. Recently, He et al. (Biochemistry 44:14055–14061,
2005) made mutants of these proteins from the wild types of protein A and protein G strains. These mutants are referred to as
protein A219 and protein G311, and it was showed that these two mutants have different 3D structures, i.e., the 3α helix bundle
structure and the (α + β) structure, respectively, despite the high sequence identity (59%). The purpose of our study was
to clarify how such 3D structural differences are coded in the sequences with high homology. To address this problem, we introduce
a predicted contact map constructed based on the interresidue average-distance statistics for prediction of folding properties
of a protein. We refer to this map as an average distance map (ADM). Furthermore, the statistics of interresidue distances
can be converted to an effective interresidue potential. We calculated the contact frequency of each residue of a protein
in random conformations with this effective interresidue potential, and then we obtained values similar to ϕ values. We refer
to this contact frequency of each residue as a p(μ) value. The comparison of the p(μ) values to the ϕ values for a protein suggests that p(μ) values reveal the information on the folding initiation site. Using these techniques, we try to extract the information
on the difference in the 3D structures of protein A219 and protein G311 coded in their amino acid sequences in the present
work. The results show that the ADM analyses and the p(μ) value analyses predict the information of folding initiation sites, which can be used to detect the 3D difference in both
proteins. 相似文献
20.
Primary Structure and Phylogenetic Relationships of a Malate Dehydrogenase Gene from Giardia lamblia
The lactate and malate dehydrogenases comprise a complex protein superfamily with multiple enzyme homologues found in eubacteria,
archaebacteria, and eukaryotes. In this study we describe the sequence and phylogenetic relationships of a malate dehydrogenase
(MDH) gene from the amitochondriate diplomonad protist, Giardia lamblia. Parsimony, distance, and maximum-likelihood analyses of the MDH protein family solidly position G. lamblia MDH within a eukaryote cytosolic MDH clade, to the exclusion of chloroplast, mitochondrial, and peroxisomal homologues. Furthermore,
G. lamblia MDH is specifically related to a homologue from Trichomonas vaginalis. This MDH topology, together with published phylogenetic analyses of β-tubulin, chaperonin 60, valyl-tRNA synthetase, and
EF-1α, suggests a sister-group relationship between diplomonads and parabasalids. Since these amitochondriate lineages contain
genes encoding proteins which are characteristic of mitochondria and α-proteobacteria, their shared ancestry suggests that
mitochondrial properties were lost in the common ancestor of both groups.
Received: 14 September 1998 / Accepted: 29 December 1998 相似文献