当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > High-affinity, peptide-specific T cell receptors can be generated by mutations in CDR1, CDR2 or CDR3.

High-affinity, peptide-specific T cell receptors can be generated by mutations in CDR1, CDR2 or CDR3.

Abstract：

:The third complementarity-determining regions (CDR3s) of antibodies and T cell receptors (TCRs) have been shown to play a major role in antigen binding and specificity. Consistent with this notion, we demonstrated previously that high-affinity, peptide-specific TCRs could be generated in vitro by mutations in the CDR3alpha region of the 2C TCR. In contrast, it has been argued that CDR1 and CDR2 are involved to a greater extent than CDR3s in the process of MHC restriction, due to their engagement of MHC helices. Based on this premise, we initiated the present study to explore whether higher affinity TCRs generated through mutations in these CDRs or other regions would lead to significant reductions in peptide specificity (i.e. the result of greater binding energy gained through interactions with major histocompatibility complex (MHC) helices). Yeast-display technology and flow sorting were used to select high-affinity TCRs from libraries of CDR mutants or random mutants. High-affinity TCRs with mutations in the first residue of the Valpha, CDR1, CDR2, or CDR3 were isolated. Unexpectedly, every TCR mutant, including those in CDR1 and CDR2, retained remarkable peptide specificity. Molecular modeling of various mutants suggested that such exquisite specificity may be due to: (1) enhanced electrostatic interactions with key peptide or MHC residues; or (2) stabilization of CDRs in specific conformations. The results indicate that the TCR is positioned so that virtually every CDR can contribute to the antigen-specificity of a T cell. The conserved diagonal docking of TCRs could thus orient each CDR loop to sense the peptide directly or indirectly through peptide-induced effects on the MHC.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Chlewicki LK,Holler PD,Monti BC,Clutter MR,Kranz DM

doi

10.1016/j.jmb.2004.11.057

keywords:

subject

Has Abstract

pub_date

2005-02-11 00:00:00

pages

223-39

issue

1

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(04)01528-1

journal_volume

346

pub_type

杂志文章

相关文献

JOURNAL OF MOLECULAR BIOLOGY文献大全
  • Two types of telomeric chromatin in Tetrahymena thermophila.

    abstract：:The telomeric d(GGGGTT).d(AACCCC) repeat tracts (G4T2 repeats) in Tetrahymena thermophila macronuclei were shown previously to be packaged in a non-nucleosomal DNA-protein complex. Here, we demonstrate that these telomeric repeats, together with a short region of the immediately adjacent non-telomeric sequence, exist ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1998.1867

    authors： Cohen P,Blackburn EH

    更新日期：1998-07-17 00:00:00

  • Ribosomal proteins L11 and L10.(L12)4 and the antibiotic thiostrepton interact with overlapping regions of the 23 S rRNA backbone in the ribosomal GTPase centre.

    abstract：:The Escherichia coli ribosomal protein (r-protein) L11 and its binding site on 23 S ribosomal RNA (rRNA) are associated with ribosomal hydrolysis of guanosine 5'-triphosphate (GTP). We have used hydroxyl radical footprinting to map the contacts between L11 and the backbone riboses in 23 S rRNA, and to investigate how ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1993.1655

    authors： Rosendahl G,Douthwaite S

    更新日期：1993-12-20 00:00:00

  • SecA, the motor of the secretion machine, binds diverse partners on one interactive surface.

    abstract：:In all living cells, regulated passage across membranes of specific proteins occurs through a universally conserved secretory channel. In bacteria and chloroplasts, the energy for the mechanical work of moving polypeptides through that channel is provided by SecA, a regulated ATPase. Here, we use site-directed spin la...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.06.049

    authors： Cooper DB,Smith VF,Crane JM,Roth HC,Lilly AA,Randall LL

    更新日期：2008-09-26 00:00:00

  • Functional interactions among the His40, Glu58 and His92 catalysts of ribonuclease T1 as studied by double and triple mutants.

    abstract：:We report on the functional interplay between the His40, Glu58 and His92 catalysts of ribonuclease T1. The kinetic properties of the single His40Ala, Glu58Ala and His92Gln mutants have been compared with those of the corresponding double and triple mutants. When His40, Glu58 and His92 are mutated separately or togethe...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1993.1078

    authors： Steyaert J,Wyns L

    更新日期：1993-02-05 00:00:00

  • Structural basis of HIV-1 activation by NF-kappaB--a higher-order complex of p50:RelA bound to the HIV-1 LTR.

    abstract：:The activation and latency of human immunodeficiency virus type 1 (HIV-1) are tightly controlled by the transcriptional activity of its long terminal repeat (LTR) region. The LTR is regulated by viral proteins as well as host factors, including the nuclear factor kappaB (NF-kappaB) that becomes activated in virus-infe...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2009.08.023

    authors： Stroud JC,Oltman A,Han A,Bates DL,Chen L

    更新日期：2009-10-16 00:00:00

  • Tandemization endows bovine pancreatic ribonuclease with cytotoxic activity.

    abstract：:Due to their ability to degrade RNA, selected members of the bovine pancreatic ribonuclease A (RNase A) superfamily are potent cytotoxins. These cytotoxic ribonucleases enter the cytosol of target cells, where they degrade cellular RNA and cause cell death. The cytotoxic activity of most RNases, however, is abolished ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2006.03.007

    authors： Leich F,Köditz J,Ulbrich-Hofman R,Arnold U

    更新日期：2006-05-19 00:00:00

  • A conformational switch involved in maturation of Staphylococcus aureus bacteriophage 80α capsids.

    abstract：:Bacteriophages are involved in many aspects of the spread and establishment of virulence factors in Staphylococcus aureus, including the mobilization of genetic elements known as S. aureus pathogenicity islands (SaPIs), which carry genes for superantigen toxins and other virulence factors. SaPIs are packaged into phag...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2010.11.047

    authors： Spilman MS,Dearborn AD,Chang JR,Damle PK,Christie GE,Dokland T

    更新日期：2011-01-21 00:00:00

  • Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.

    abstract：:MEF2 and NKX2-5 transcription factors interact with each other in cardiogenesis and are necessary for normal heart formation. Despite evidence suggesting that these two transcription factors function synergistically and possibly through direct physical interactions, molecular mechanisms by which they interact are not ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2020.07.004

    authors： Lei X,Zhao J,Sagendorf JM,Rajashekar N,Xu J,Dantas Machado AC,Sen C,Rohs R,Feng P,Chen L

    更新日期：2020-09-04 00:00:00

  • Analysis of the distribution of binding sites for a tissue-specific transcription factor in the vertebrate genome.

    abstract：:Hepatocyte nuclear factor 1 (HNF1) is a dimeric homeoprotein expressed in hepatocytes and in a few other epithelial cells where it helps regulate the expression of a specific subset of genes. In an attempt to identify novel target genes for HNF1 and to assess the distribution of its target sites within the vertebrate ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0760

    authors： Tronche F,Ringeisen F,Blumenfeld M,Yaniv M,Pontoglio M

    更新日期：1997-02-21 00:00:00

  • Crystallographic structure of a PLP-dependent ornithine decarboxylase from Lactobacillus 30a to 3.0 A resolution.

    abstract：:Ornithine decarboxylase from Lactobacillus 30a (L30a OrnDC) is representative of the large, pyridoxal-5'-phosphate-dependent decarboxylases that act on lysine, arginine or ornithine. The crystal structure of the L30a OrnDC has been solved to 3.0 A resolution using MIR phases in combination with density modification (s...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1995.0526

    authors： Momany C,Ernst S,Ghosh R,Chang NL,Hackert ML

    更新日期：1995-10-06 00:00:00

  • Structure of Mutant Hepatitis B Core Protein Capsids with Premature Secretion Phenotype.

    abstract：:Hepatitis B virus is a major human pathogen that consists of a viral genome surrounded by an icosahedrally ordered core protein and a polymorphic, lipidic envelope that is densely packed with surface proteins. A point mutation in the core protein in which a phenylalanine at position 97 is exchanged for a smaller leuci...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2018.10.018

    authors： Böttcher B,Nassal M

    更新日期：2018-12-07 00:00:00

  • Structural analysis of CYP2R1 in complex with vitamin D3.

    abstract：:The activation of vitamin D to its hormonal form is mediated by cytochrome P450 enzymes. CYP2R1 catalyzes the initial step converting vitamin D into 25-hydroxyvitamin D. A CYP2R1 gene mutation causes an inherited form of rickets due to 25-hydroxylase deficiency. To understand the narrow substrate specificity of CYP2R1...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2008.03.065

    authors： Strushkevich N,Usanov SA,Plotnikov AN,Jones G,Park HW

    更新日期：2008-06-27 00:00:00

  • Point mutations that lock Salmonella typhimurium flagellar filaments in the straight right-handed and left-handed forms and their relation to filament superhelicity.

    abstract：:We have determined the nucleotide sequence of two mutant and the parent fliC genes, encoding the protein flagellin (serotype i), of Salmonella typhimurium. The flagellar filaments of the two mutants, SJW1655 and SJW1660, are locked in the straight-right-handed (R) and straight-left-handed (L) conformations, respective...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(91)90382-g

    authors： Hyman HC,Trachtenberg S

    更新日期：1991-07-05 00:00:00

  • 2.5 A structure of aspartate carbamoyltransferase complexed with the bisubstrate analog N-(phosphonacetyl)-L-aspartate.

    abstract：:In an X-ray diffraction study using the method of multiple isomorphous replacement, the structure of aspartate carbamoyltransferase (EC 2.1.3.2) complexed with the bisubstrate analog N-(phosphonacetyl)-L-aspartate (PALA) has been solved to 2.5 A. Ten rounds of model building and 123 cycles of restrained reciprocal spa...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(87)90265-8

    authors： Krause KL,Volz KW,Lipscomb WN

    更新日期：1987-02-05 00:00:00

  • An EM view of the FokI synaptic complex by single particle analysis.

    abstract：:FokI is a type IIS restriction endonuclease that recognizes the 5'-GGATG-3' sequence and cleaves non-specifically at 9 and 13 base-pairs away on the top and bottom strands, respectively, to produce a 5' overhang. FokI is a bipartite endonuclease with separate recognition and cleavage domains. Because of its bipartite ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2007.04.066

    authors： Vanamee ES,Berriman J,Aggarwal AK

    更新日期：2007-07-06 00:00:00

  • Bulge-induced bends in RNA: quantification by transient electric birefringence.

    abstract：:Bulges represent one of the most common non-helical elements in RNA, often displaying a strong degree of phylogenetic conservation, both in location and sequence, within larger RNA molecules. Thus, knowledge of the conformation and flexibility of RNA bulges is an important prerequisite for understanding the rules gove...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1995.0155

    authors： Zacharias M,Hagerman PJ

    更新日期：1995-03-31 00:00:00

  • Recruiting Zn2+ to mediate potent, specific inhibition of serine proteases.

    abstract：:As regulators of ubiquitous biological processes, serine proteases can cause disease states when inappropriately expressed or regulated, and are thus rational targets for inhibition by drugs. Recently we described a new inhibition mechanism applicable for the development of potent, selective small molecule serine prot...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1999.3071

    authors： Katz BA,Luong C

    更新日期：1999-09-24 00:00:00

  • The structure of Escherichia coli cytosine deaminase.

    abstract：:Cytosine deaminase (CD) catalyzes the deamination of cytosine, producing uracil. This enzyme is present in prokaryotes and fungi (but not multicellular eukaryotes) and is an important member of the pyrimidine salvage pathway in those organisms. The same enzyme also catalyzes the conversion of 5-fluorocytosine to 5-flu...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2001.5277

    authors： Ireton GC,McDermott G,Black ME,Stoddard BL

    更新日期：2002-01-25 00:00:00

  • Mechanism of strand cleavage and exchange in the Cre-lox site-specific recombination system.

    abstract：:The bacteriophage P1 recombinase Cre mediates site-specific recombination between loxP sites. The loxP site consists of two 13 base-pair inverted repeats separated by an eight base-pair spacer region. When DNA containing the loxP site is incubated with Cre, specific cleavages occur within the spacer region, creating a...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(85)90224-4

    authors： Hoess RH,Abremski K

    更新日期：1985-02-05 00:00:00

  • Processive DNA Unwinding by RecBCD Helicase in the Absence of Canonical Motor Translocation.

    abstract：:Escherichia coli RecBCD is a DNA helicase/nuclease that functions in double-stranded DNA break repair. RecBCD possesses two motors (RecB, a 3' to 5' translocase, and RecD, a 5' to 3' translocase). Current DNA unwinding models propose that motor translocation is tightly coupled to base pair melting. However, some bioch...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2016.07.002

    authors： Simon MJ,Sokoloski JE,Hao L,Weiland E,Lohman TM

    更新日期：2016-07-31 00:00:00

  • Pro-sequence assisted folding and disulfide bond formation of human nerve growth factor.

    abstract：:Nerve growth factor (NGF) is a member of the neurotrophin family. These growth factors support neuronal survival and differentiation. Neurotrophins are synthesized as pre-pro-proteins. Whereas the pre-sequences mediate secretion, the function of the pro-peptides is largely unknown. To test the role of the pro-sequence...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.2000.4295

    authors： Rattenholl A,Ruoppolo M,Flagiello A,Monti M,Vinci F,Marino G,Lilie H,Schwarz E,Rudolph R

    更新日期：2001-01-19 00:00:00

  • Low resolution crystal structure of muconolactone isomerase. A decamer with a 5-fold symmetry axis.

    abstract：:Muconolactone isomerase from Pseudomonas putida crystallizes from sodium sulfate solution in space group P2(1) (a = 65.84 A, b = 105.70 A, c = 77.20 A, beta = 90.5 degrees) with ten 11,000 Mr subunits per asymmetric unit. The 7 A resolution crystal structure was solved by single isomorphous replacement followed by 10-...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(85)90382-1

    authors： Katz BA,Ollis D,Wyckoff HW

    更新日期：1985-07-20 00:00:00

  • Integrative modelling coupled with ion mobility mass spectrometry reveals structural features of the clamp loader in complex with single-stranded DNA binding protein.

    abstract：:DNA polymerase III, a decameric 420-kDa assembly, simultaneously replicates both strands of the chromosome in Escherichia coli. A subassembly of this holoenzyme, the seven-subunit clamp loader complex, is responsible for loading the sliding clamp (β2) onto DNA. Here, we use structural information derived from ion mobi...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2013.04.006

    authors： Politis A,Park AY,Hall Z,Ruotolo BT,Robinson CV

    更新日期：2013-11-29 00:00:00

  • Secondary structure and thermostability of the phage P22 tailspike. XX. Analysis by Raman spectroscopy of the wild-type protein and a temperature-sensitive folding mutant.

    abstract：:The thermostable tailspike endorhamnosidase of bacteriophage P22 has been investigated by laser Raman spectroscopy to determine the protein's secondary structure and the basis of its thermostability. The conformation of the native tailspike, determined by Raman amide I and amide III band analyses, is 52 to 61% beta-sh...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(88)90620-1

    authors： Sargent D,Benevides JM,Yu MH,King J,Thomas GJ Jr

    更新日期：1988-02-05 00:00:00

  • Reduced misreading of asparagine codons by Escherichia coli tRNALys with hypomodified derivatives of 5-methylaminomethyl-2-thiouridine in the wobble position.

    abstract：:It has been suggested that modified nucleosides of the xm5(s2)U(m)34-type restrict the wobble capacity of the base, and that their function is to prevent misreading in the third position of the codon in mixed codon family boxes that encode two different amino acids. In this study in Escherichia coli, the misreading in...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1998.2162

    authors： Hagervall TG,Pomerantz SC,McCloskey JA

    更新日期：1998-11-20 00:00:00

  • 3D gene of foot-and-mouth disease virus. Conservation by convergence of average sequences.

    abstract：:The nucleotide sequence of the 3D (polymerase) gene of eight epidemiologically related isolates of foot-and-mouth disease virus of serotype C1 is reported. The genetic heterogeneity of 3D RNA is compared with that of the VP1-coding RNA of the same viruses. Regression lines of substitutions per nucleotide that distingu...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(88)90367-1

    authors： Villaverde A,Martínez-Salas E,Domingo E

    更新日期：1988-12-05 00:00:00

  • A model for the mechanism of polymerase translocation.

    abstract：:A general mechanism for polymerase translocation is elaborated. The central feature of this mechanism is that a rapid translocational equilibrium is established after each cycle of nucleoside monophosphate incorporation such that the polymerase distributes itself by diffusional sliding between all accessible positions...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1006/jmbi.1996.0707

    authors： Guajardo R,Sousa R

    更新日期：1997-01-10 00:00:00

  • Control of ColE1 plasmid replication. Intermediates in the binding of RNA I and RNA II.

    abstract：:Replication of plasmid ColE1 is regulated by a plasmid-specified small RNA (RNA I). RNA I binds to the precursor (RNA II) of the primer for DNA synthesis and inhibits primer formation. The process of binding of RNA I to RNA II that results in formation of a stably bound complex consists of a series of reactions formin...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(90)90230-j

    authors： Tomizawa J

    更新日期：1990-04-20 00:00:00

  • Bacteriophage P2 late promoters. II. Comparison of the four late promoter sequences.

    abstract：:The late genes of bacteriophage P2 are clustered into four transcription units. We have reported the transcription initiation sites for two of the late messenger RNAs, encoding genes QP and ONMLKRS. We have now located the 5' ends of the two remaining late mRNAs. The first gene in the VJHG transcription unit has been ...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/0022-2836(85)90226-8

    authors： Christie GE,Calendar R

    更新日期：1985-02-05 00:00:00

  • DNA topology and geometry in Flp and Cre recombination.

    abstract：:The Flp recombinase of yeast and the Cre recombinase of bacteriophage P1 both belong to the lambda-integrase (Int) family of site-specific recombinases. These recombination systems recognize recombination-target sequences that consist of two 13bp inverted repeats flanking a 6 or 8bp spacer sequence. Recombination reac...

    journal_title：Journal of molecular biology

    pub_type： 杂志文章

    doi：10.1016/j.jmb.2006.01.037

    authors： Vetcher AA,Lushnikov AY,Navarra-Madsen J,Scharein RG,Lyubchenko YL,Darcy IK,Levene SD

    更新日期：2006-04-07 00:00:00