Abstract：
:Proteasomes, major proteolytic sites in eukaryotic cells, play an important part in major histocompatibility class I (MHC I) ligand generation and thus in the regulation of specific immune responses. Their cleavage specificity is of outstanding interest for this process. In order to generalize previously determined cleavage motifs of 20 S proteasomes, we developed network-based model proteasomes trained by an evolutionary algorithm with experimental cleavage data of yeast and human 20 S proteasomes. A window of ten flanking amino acid residues proved sufficient for the model proteasomes to reproduce the experimental results with 98-100 % accuracy. Actual experimental data were reproduced significantly better than randomly selected cleavage sites, suggesting that our model proteasomes were able to extract rules inherent to proteasomal cleavage data. The affinity parameters of the model, which decide for or against cleavage, correspond with the cleavage motifs determined experimentally. The predictive power of the model was verified for unknown (to the program) test conditions: the prediction of cleavage numbers in proteins and the generation of MHC I ligands from short peptides. In summary, our model proteasomes reproduce and predict proteasomal cleavages with high degree of accuracy. They present a promising approach for predicting proteasomal cleavage products in future attempts and, in combination with existing algorithms for MHC I ligand prediction, will be tested to improve cytotoxic T lymphocyte epitope prediction.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Kuttler C,Nussbaum AK,Dick TP,Rammensee HG,Schild H,Hadeler KPdoi
10.1006/jmbi.2000.3683keywords:
subject
Has Abstractpub_date
2000-05-05 00:00:00pages
417-29issue
3eissn
0022-2836issn
1089-8638pii
S0022-2836(00)93683-0journal_volume
298pub_type
杂志文章abstract：:We have determined the X-ray crystallographic structure of trout Hb I in both the deoxy and carbonmonoxy forms to resolution limits of 2.3 angstroms and 2.5 angstroms, respectively. The overall fold of the molecule is highly similar to that of human HbA despite the low level of sequence identity between these proteins...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0355
更新日期：1996-06-21 00:00:00
abstract：:Two new human cDNAs, designated phclk2 and phclk3, which have a high identity to the cDNA of the human protein kinase clk, were characterized. Typical features of hclk2 and hclk3 proteins are non-homologous N-terminal regions and the presence of the C-terminal protein kinase domain, which is characteristic for serine/...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1763
更新日期：1994-12-16 00:00:00
abstract：:Interactions of polymerase X from African swine fever virus with single-stranded DNA (ssDNA) have been studied, using quantitative fluorescence titration and analytical ultracentrifugation techniques. Experiments were performed with a fluorescent etheno-derivative of ssDNA oligomers. Studies of unmodified ssDNA oligom...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.10.061
更新日期：2006-02-10 00:00:00
abstract：:Iron loss in vitro by the iron scavenger bovine lactoferrin was investigated in acidic media in the presence of three different monoanions (NO(3)(-), Cl(-) and Br(-)) and one dianion (SO(4)(2-)). Holo and monoferric C-site lactoferrins lose iron in acidic media (pH< or =3.5) by a four-step mechanism. The first two ste...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4101
更新日期：2000-10-20 00:00:00
abstract：:The role of the sigma 70 subunit of Escherichia coli RNA polymerase in transcription activation by positive transcription factors was investigated. For this purpose, we constructed a nested set of E. coli rpoD deletion mutants generating carboxy-terminally truncated sigma 70 subunits of RNA polymerase in a high-expres...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1001
更新日期：1994-01-14 00:00:00
abstract：:Transcription of the Bacillus subtilis iol divergon is negatively regulated by a repressor encoded by iolR, which belongs to the DeoR family of bacterial regulators. Gel retardation analysis involving the IolR protein synthesized in Escherichia coli revealed that IolR bound specifically and independently to each of th...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2398
更新日期：1999-01-22 00:00:00
abstract：:The mercury resistance locus encoded by Tn21 on the monocopy IncFII plasmid R100 (merTn21) consists of a metal-responsive activator/repressor, merR, which controls initiation of a polycistronic message that includes genes for the uptake (merTPC) and reduction (merA) of Hg2+ and merD, which may also play a minor regula...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(92)90919-b
更新日期：1992-05-20 00:00:00
abstract：:The termination signal that limits transcription through the early region of bacteriophage T3 (T3Te) has been cloned and sequenced. The nucleotide sequence of T3Te is identical with that of T7Te, with the exception of a single G to U substitution in the 3' tail of the terminated transcript, and addition of an AC to th...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(87)90456-6
更新日期：1987-11-05 00:00:00
abstract：:The Mycobacterium leprae RuvA homologue (MlRuvA) was over-expressed in Escherichia coli and purified to homogeneity. The DNA-binding specificity and the functional interactions of MlRuvA with E. coli RuvB and RuvC (EcRuvB and EcRuvC) were examined using synthetic Holliday junctions. MlRuvA bound specifically to Hollid...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4009
更新日期：2000-08-25 00:00:00
abstract：:The rotavirus double-layered particle (DLP) is a molecular machine that transcribes 11 genomic segments of double-stranded RNA into full-length mRNA segments during viral replication. DLPs from the human Wa strain of virus, belonging to subgroup II (SG II), possess a significantly reduced level of transcriptase activi...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.11.049
更新日期：2006-02-10 00:00:00
abstract：:We have examined expression of the lambdacI operon in single cells via a rex Colon, two colons gfp substitution. Although average fluorescence agreed with expectations for expression of lambda-repressor, fluorescence fluctuated greatly from cell-to-cell. Fluctuations in repressor concentration are not predicted by pre...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2003.09.037
更新日期：2003-11-28 00:00:00
abstract：:Oligonucleotides can bind to double-stranded DNA in a sequence-specific manner to form triple helices. Uniformly modified, pyrimidine-rich oligodeoxyribonuclotides containing internucleosidic N3'-P5' phosphoramidate linkages are known to form very stable triplexes with their DNA target. Psoralen-conjugated triple heli...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4386
更新日期：2001-02-09 00:00:00
abstract：:Sleeping Beauty (SB) is the most active Tc1/mariner-type transposable element in vertebrates, and is therefore a valuable vector for transposon mutagenesis in vertebrate models and for human gene therapy. We have analyzed factors affecting target site selection of SB in mammalian cells, by generating transposition eve...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)00991-9
更新日期：2002-10-25 00:00:00
abstract：:The crystal structure of the ferredoxin:NADP+ reductase (FNR) from the cyanobacterium Anabaena PCC 7119 has been determined at 2.6 A resolution by multiple isomorphous replacement and refined using 15.0 A to 1.8 A data, collected at 4 degrees C, to an R-factor of 0.172. The model includes 303 residues, the flavin aden...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0553
更新日期：1996-10-18 00:00:00
abstract：:The tyrosyl-tRNA synthetases from Bacillus stearothermophilus (Bst-TyrTS) and Escherichia coli (Eco-TyrTS) are 56% identical in amino acid sequence. To map and characterize the set of interactions that makes Bst-TyrTS more stable than Eco-TyrTS, a family of nine hybrid proteins was constructed between the two enzymes....
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1993.1575
更新日期：1993-11-05 00:00:00
abstract：:We have constructed complexes of ribosomal proteins S8, S15, S8 + S15 and S8 + S15 + S6 + S18 with 16 S ribosomal RNA, and probed the RNA moiety with a set of structure-specific chemical and enzymatic probes. Our results show the following effects of assembly of proteins on the reactivity of specific nucleotides in 16...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(88)90242-2
更新日期：1988-03-20 00:00:00
abstract：:Numerous mitochondrial quality control mechanisms exist within cells, but none have been shown to effectively assess and control the quality of mitochondrial DNA (mtDNA). One reason such mechanisms have yet to be elucidated is that they do not appear to be particularly active in most somatic cells, where many studies ...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2018.10.019
更新日期：2018-12-07 00:00:00
abstract：:A random coil-helix transition underlies the association of the presynaptic protein α-synuclein (αS) with curved vesicle membranes to fold Asp2-Ala89 into a continuous helix. To clarify this transition, we examined αS folding cooperativity, helix nucleation and propagation in relation to membrane stabilization and lea...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2014.02.024
更新日期：2014-05-15 00:00:00
abstract：:Single crystals of glycosylated recombinant human renin have been obtained using the hanging-drop vapor diffusion method with polyethylene glycol and sodium chloride as coprecipitants. The crystals belong to the cubic space group P2(1)3 with a = 143.0 A and contain two molecules of renin in the asymmetric unit. A self...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(89)90305-7
更新日期：1989-11-05 00:00:00
abstract：:Lysine methylation is a key regulator of protein-protein binding. The amine group of lysine can accept up to three methyl groups, and experiments show that protein-protein binding free energies are sensitive to the extent of methylation. These sensitivities have been rationalized in terms of chemical and structural fe...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2020.166745
更新日期：2021-02-05 00:00:00
abstract：:Tumor suppressor p53 plays a central role in tumor suppression. p53 is the most frequently mutated gene in human cancer, and over half of human cancers contain p53 mutations. Majority of p53 mutations in cancer are missense mutations, leading to the expression of full-length mutant p53 (mutp53) protein. While the crit...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2017.03.030
更新日期：2017-06-02 00:00:00
abstract：:Using a clone characterized in the course of a random sequencing programme of Arabidopsis thaliana, two cDNAs encoding plant type cytosolic NADPH-dependent thioredoxin reductase (NTR) have been isolated. Their sequence homology with Escherichia coli NRT (the only thioredoxin reductase of known primary structure) is ab...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.1091
更新日期：1994-01-28 00:00:00
abstract：:Ca2+ concentration jumps for the activation of Ca2+-dependent ion channels or transporters can be obtained either by fast solution exchange or by the use of caged Ca2+. Here, we report on an alternate optogenetic method for the activation of Ca2+ and voltage-dependent large conductance (BK) potassium channels. This wa...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2017.02.004
更新日期：2017-03-24 00:00:00
abstract：:Although DNA methylation is a fundamental mechanism for repressing genetic activity, the influence of methyl groups on DNA conformation is found to be small. In this study, the role of cytosine methylation is analysed in the context of DNA condensation by examining its influence on DNA-DNA recognition processes. Previ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1997.1137
更新日期：1997-07-18 00:00:00
abstract：:The NusA transcription elongation protein, which binds RNA, contains sequences corresponding to the S1 and KH classes of identified RNA binding domains. An essential function in E. coli, NusA is also one of the host factors required for action of the N transcription antitermination protein of lambda. Tandem KH domains...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)00238-3
更新日期：2002-05-17 00:00:00
abstract：:The intracellular ileal lipid binding proteins (ILBPs) are involved in the transport and enterohepatic circulation of bile acids. ILBPs from different species show high sequence and structural homology and have been shown to bind multiple bile acid ligands with differing degrees of selectivity and positive co-operativ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.06.024
更新日期：2007-08-31 00:00:00
abstract：:The primary goal of this study was to gain a better understanding of the effect of environment and ionic strength on the pK values of histidine residues in proteins. The salt-dependence of pK values for two histidine residues in ribonuclease Sa (RNase Sa) (pI=3.5) and a variant in which five acidic amino acids have be...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(02)01274-3
更新日期：2003-01-31 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mediator of angiogenesis and vasculogenesis. VEGF is involved pathologically in cancer, proliferative retinopathy and rheumatoid arthritis, and as such represents an important therapeutic target. Three classes of disulfide-constrained pept...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5370
更新日期：2002-02-22 00:00:00
abstract：:Drugs can affect function in proteins by modulating their flexibility. Despite this possibility, there are very few studies on how drug binding affects the dynamics of target macromolecules. FKBP12 (FK506 binding protein 12) is a prolyl cis-trans isomerase and a drug target. The immunosuppressant drug rapamycin exerts...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2010.10.037
更新日期：2011-01-14 00:00:00
abstract：:Chagasin is a protein produced by Trypanosoma cruzi, the parasite that causes Chagas' disease. This small protein belongs to a recently defined family of cysteine protease inhibitors. Although resembling well-known inhibitors like the cystatins in size (110 amino acid residues) and function (they all inhibit papain-li...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.05.005
更新日期：2007-08-03 00:00:00
