The I binding specificity of human VH 4-34 (VH 4-21) encoded antibodies is determined by both VH framework region 1 and complementarity determining region 3.


:Essentially all cold agglutinins (CA) with red blood cell I/i specificity isolated from patients with CA disease stemming from lymphoproliferative disorders utilize the VH 4-34 (VH 4-21) gene segment. This near universality of the restricted use of a single gene segment is substantially greater than that demonstrated for other autoantibodies. The monoclonal antibody 9G4 exclusively binds VH 4-34 encoded antibodies and serves as a marker for the VH 4-34 gene segment. Previous studies form our laboratory localized the 9G4 reactive area to framework region 1 (FR1). In the present study, the relative roles of VH FR1, heavy (H) chain complementarity determining region 3 (CDRH 3) and the light (L) chain in I antigen binding were investigated. Mutants containing FR1 sequences from the other VH families, CDRH 3 exchanges, and combinatorial antibodies involving L chain interchanges were produced in the baculovirus system and tested in an I binding assay. The data indicate that FR1 of the VH 4-34 gene segment and the CDRH 3 are essential for the interaction between CA and the I antigen, with the CDRH 3 being fundamental in determining the fine specificity of antigen binding (I versus i). Mutants with substantially altered CDRH 1 and CDRH 2 regions bind I as long as the FR1 is VH 4-34 encoded and the CDRH 3 has a permissive sequence. Light chain swaps indicate that even though antigen binding is predominantly mediated by the H chain, the association with antigen can be abrogated by an incompatible L chain. The necessity for VH 4-34 FR1 explains the almost exclusive use of the VH 4-34 gene segment in cold agglutinins. We hypothesize that, as a general phenomenon, the H chain FR1 of many antibodies may be important in providing the contact required for the close association of antibody with antigen, while the CDRH 3 dictates the fine specificity and strenght of binding.


J Mol Biol


Li Y,Spellerberg MB,Stevenson FK,Capra JD,Potter KN




Has Abstract


1996-03-01 00:00:00














  • Probing the assembly of the 3' major domain of 16 S rRNA. Interactions involving ribosomal proteins S2, S3, S10, S13 and S14.

    abstract::We have used rapid probing methods to follow the changes in reactivity of residues in 16 S rRNA to chemical and enzymatic probes as ribosomal proteins S2, S3, S10, S13 and S14 are assembled into 30 S subunits. Effects observed are confined to the 3' major domain of the RNA and comprise three general classes. (1) Monos...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Powers T,Stern S,Changchien LM,Noller HF

    更新日期:1988-06-20 00:00:00

  • 1.8 A crystal structure of the major NAD(P)H:FMN oxidoreductase of a bioluminescent bacterium, Vibrio fischeri: overall structure, cofactor and substrate-analog binding, and comparison with related flavoproteins.

    abstract::We have solved the crystal structure of FRase I, the major NAD(P)H:FMN oxidoreductase of Vibrio fischeri, by the multiple isomorphous replacement method (MIR) at 1.8 A resolution with the conventional R factor of 0.187. The crystal structure of FRase I complexed with its competitive inhibitor, dicoumarol, has also bee...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Koike H,Sasaki H,Kobori T,Zenno S,Saigo K,Murphy ME,Adman ET,Tanokura M

    更新日期:1998-07-10 00:00:00

  • Rubredoxin from Desulfovibrio gigas. A molecular model of the oxidized form at 1.4 A resolution.

    abstract::The crystal structure of rubredoxin from the sulfate-reducing bacterium Desulfovibrio gigas has been determined at 1.4 A resolution (1 A = 0.1 nm) by X-ray diffraction methods; starting with a model of the isostructural rubredoxin from Desulfovibrio vulgaris. Refinement of the molecular model has been carried out by r...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Frey M,Sieker L,Payan F,Haser R,Bruschi M,Pepe G,LeGall J

    更新日期:1987-10-05 00:00:00

  • Unassigned or nonsense codons in Micrococcus luteus.

    abstract::We previously reported that in Micrococcus luteus, a Gram-positive eubacterium with high genomic G + C content, certain codons ending with A did not appear in coding frames, including termination sites, and tRNAs that translate these codons were not detected. These facts suggest that at least some of them are unassign...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Kano A,Ohama T,Abe R,Osawa S

    更新日期:1993-03-05 00:00:00

  • Transcription inhibition induced by modified triple helix-forming oligonucleotides: a quantitative assay for evaluation in cells.

    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


    authors: Faria M,Wood CD,White MR,Hélène C,Giovannangeli C

    更新日期:2001-02-09 00:00:00

  • Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism.

    abstract::The structure of Mycobacterium tuberculosis dUTP nucleotidohydrolase (dUTPase) has been determined at 1.3 Angstrom resolution in complex with magnesium ion and the non-hydrolyzable substrate analog, alpha,beta-imido dUTP. dUTPase is an enzyme essential for depleting potentially toxic concentrations of dUTP in the cell...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Chan S,Segelke B,Lekin T,Krupka H,Cho US,Kim MY,So M,Kim CY,Naranjo CM,Rogers YC,Park MS,Waldo GS,Pashkov I,Cascio D,Perry JL,Sawaya MR

    更新日期:2004-08-06 00:00:00

  • Domain closure mechanism in transferrins: new viewpoints about the hinge structure and motion as deduced from high resolution crystal structures of ovotransferrin N-lobe.

    abstract::The crystal structure of holo hen ovotransferrin N-lobe refined at 1.65 A resolution has been obtained. The final model gave an R-factor of 0.173 in the resolution range between 10.0 and 1.65 A. The comparison of the structure with previous high-resolution apo and Fe(3+)-loaded, domain-opened intermediate structures p...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Mizutani K,Mikami B,Hirose M

    更新日期:2001-06-15 00:00:00

  • Fast Translation within the First 45 Codons Decreases mRNA Stability and Increases Premature Transcription Termination in E. coli.

    abstract::We show here that the specific use of fast or slowly translated codons in the early coding region of a gene may influence both the mRNA stability and premature transcription termination. We first inserted a pair of nearly identical 42-base-pair (bp)-long sequences into codon 3 of the Escherichia coli lacZ gene. The on...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Pedersen S,Terkelsen TB,Eriksen M,Hauge MK,Lund CC,Sneppen K,Mitarai N

    更新日期:2019-03-15 00:00:00

  • Manganese water-soluble porphyrin senses DNA conformation.

    abstract::We have determined the sites that are preferentially cleaved by Mn(T4MPyP) (where T4MPyP is the dianion of 5, 10, 15, 20, tetrakis (4-N-methylpyridine)porphyrin) on synthetic DNAs and on both intrinsically curved and average-shaped natural DNA sequences. On the basis of cleavage selectivity and of DNase I footprinting...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Di Mauro E,Saladino R,Tagliatesta P,De Sanctis V,Negri R

    更新日期:1998-09-11 00:00:00

  • Angular disorder in actin: is it consistent with general principles of protein structure?

    abstract::Harold Erickson has recently provided a useful analysis of helical structures having one class versus two classes of intersubunit bonds. His analysis is based upon an assumption that the subunits themselves are essentially unchanged upon bond formation (polymerization). He shows that such a structure having two classe...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Egelman EH,DeRosier DJ

    更新日期:1991-02-05 00:00:00

  • Simian virus 40 illegitimate recombination occurs near short direct repeats.

    abstract::We have analysed nucleotide sequences at the junction between simian virus 40 (SV40) and cellular DNA in the Fisher rat transformed line tsA30-N2. This line contains a single insertion of one complete SV40 genome with a terminal duplication of 267 nucleotides, the recombination sites being located at nucleotides 439 a...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Hasson JF,Mougneau E,Cuzin F,Yaniv M

    更新日期:1984-07-25 00:00:00

  • Insights into RNA virus mutant spectrum and lethal mutagenesis events: replicative interference and complementation by multiple point mutants.

    abstract::RNA virus behavior can be influenced by interactions among viral genomes and their expression products within the mutant spectra of replicating viral quasispecies. Here, we report the extent of interference of specific capsid and polymerase mutants of foot-and-mouth disease virus (FMDV) on replication of wild-type (wt...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Perales C,Mateo R,Mateu MG,Domingo E

    更新日期:2007-06-15 00:00:00

  • On itinerant water molecules and detectability of protein-protein interfaces through comparative analysis of homologues.

    abstract::We discuss the question of which residues are sufficiently important for protein-protein interaction to be under notable evolutionary pressure. Its interest stems from the applicability of this knowledge in the reverse direction, to detect a protein-protein interface on a single protomer, starting from the rate of mut...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Mihalek I,Res I,Lichtarge O

    更新日期:2007-06-01 00:00:00

  • Burst-phase expansion of native protein prior to global unfolding in SDS.

    abstract::Although numerous studies have been directed at understanding early folding events through the characterization of folding intermediates, there are few reports on the very late folding events, i.e. on the events taking place on the native side of the folding barrier and on alternative conformations of the folded state...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Otzen DE,Oliveberg M

    更新日期:2002-02-01 00:00:00

  • Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function.

    abstract::Mutations at solvent-inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understo...

    journal_title:Journal of molecular biology

    pub_type: 评论,杂志文章


    authors: Lee SY,Pullen L,Virgil DJ,Castañeda CA,Abeykoon D,Bolon DN,Fushman D

    更新日期:2014-04-03 00:00:00

  • Ribonuclease T1 with free recognition and catalytic site: crystal structure analysis at 1.5 A resolution.

    abstract::The free form of ribonuclease T1 (RNase T1) has been crystallized at neutral pH, and the three-dimensional structure of the enzyme has been determined at 1.5 A nominal resolution. Restrained least-squares refinement yielded an R value of 14.3% for 12,623 structure amplitudes. The high resolution of the structure analy...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Martinez-Oyanedel J,Choe HW,Heinemann U,Saenger W

    更新日期:1991-11-20 00:00:00

  • Crystal structures of the complexes between vancomycin and cell-wall precursor analogs.

    abstract::The crystal structures of three vancomycin complexes with two vancomycin-sensitive cell-wall precursor analogs (diacetyl-Lys-D-Ala-D-Ala and acetyl-D-Ala-D-Ala) and a vancomycin-resistant cell-wall precursor analog (diacetyl-Lys-D-Ala-D-lactate) were determined at atomic resolutions of 1.80 A, 1.07 A, and 0.93 A, resp...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Nitanai Y,Kikuchi T,Kakoi K,Hanamaki S,Fujisawa I,Aoki K

    更新日期:2009-02-06 00:00:00

  • Observing membrane protein diffusion at subnanometer resolution.

    abstract::Single sodium-driven rotors from a bacterial ATP synthase were embedded into a lipid membrane and observed in buffer solution at subnanometer resolution using atomic force microscopy (AFM). Time-lapse AFM topographs show the movement of single proteins within the membrane. Subsequent analysis of their individual traje...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Müller DJ,Engel A,Matthey U,Meier T,Dimroth P,Suda K

    更新日期:2003-04-11 00:00:00

  • Isolation of human antibody repertoires with preservation of the natural heavy and light chain pairing.

    abstract::The humoral immune system in higher vertebrates is unique in its ability to generate highly diverse antibody responses against most pathogens as well as against certain malignancies. Several technologies have been developed to exploit this vast source of potentially therapeutic antibodies, including hybridoma technolo...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Meijer PJ,Andersen PS,Haahr Hansen M,Steinaa L,Jensen A,Lantto J,Oleksiewicz MB,Tengbjerg K,Poulsen TR,Coljee VW,Bregenholt S,Haurum JS,Nielsen LS

    更新日期:2006-05-05 00:00:00

  • Identification of an epitope in the C terminus of normal prion protein whose expression is modulated by binding events in the N terminus.

    abstract::We have characterized the epitopes of a panel of 12 monoclonal antibodies (Mabs) directed to normal human cellular prion protein (PrP(C)) using ELISA and Western blotting of recombinant PrP or synthetic peptide fragments of PrP. The first group of antibodies, which is represented by Mabs 5B2 and 8B4, reacts with PrP(2...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Li R,Liu T,Wong BS,Pan T,Morillas M,Swietnicki W,O'Rourke K,Gambetti P,Surewicz WK,Sy MS

    更新日期:2000-08-18 00:00:00

  • Protein-DNA interactions: amino acid conservation and the effects of mutations on binding specificity.

    abstract::We investigate the conservation of amino acid residue sequences in 21 DNA-binding protein families and study the effects that mutations have on DNA-sequence recognition. The observations are best understood by assigning each protein family to one of three classes: (i) non-specific, where binding is independent of DNA ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Luscombe NM,Thornton JM

    更新日期:2002-07-26 00:00:00

  • Multi-scale sequence correlations increase proteome structural disorder and promiscuity.

    abstract::Numerous experiments demonstrate a high level of promiscuity and structural disorder in organismal proteomes. Here, we ask the question what makes a protein promiscuous, that is, prone to nonspecific interactions, and structurally disordered. We predict that multi-scale correlations of amino acid positions within prot...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Afek A,Shakhnovich EI,Lukatsky DB

    更新日期:2011-06-10 00:00:00

  • Membrane biogenesis of subunit II of cytochrome bo oxidase: contrasting requirements for insertion of N-terminal and C-terminal domains.

    abstract::The membrane assembly of the respiratory complexes requires the membrane insertases Oxa1 in mitochondria and YidC in bacteria. Oxa1 is responsible for the insertion of the mitochondrial cytochrome c oxidase subunit II (CoxII). Here, we investigated whether YidC, the bacterial Oxa1 homolog, plays a crucial role in the ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Celebi N,Yi L,Facey SJ,Kuhn A,Dalbey RE

    更新日期:2006-04-14 00:00:00

  • Three-dimensional solution structure of the thrombin-binding DNA aptamer d(GGTTGGTGTGGTTGG).

    abstract::The DNA oligonucleotide d(GGTTGGTGTGGTTGG) (thrombin aptamer) binds to thrombin and inhibits its enzymatic activity in the chain of reactions that lead to blood clotting. Two-dimensional 1H NMR studies indicate that the oligonucleotide forms a folded structure in solution, composed of two guanine quartets connected by...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Schultze P,Macaya RF,Feigon J

    更新日期:1994-02-04 00:00:00

  • Molecular model of an alpha-helical prion protein dimer and its monomeric subunits as derived from chemical cross-linking and molecular modeling calculations.

    abstract::Prions are the agents of a series of lethal neurodegenerative diseases. They are composed largely, if not entirely, of the host-encoded prion protein (PrP), which can exist in the cellular isoform PrP(C) and the pathological isoform PrP(Sc). The conformational change of the alpha-helical PrP(C) into beta-sheet-rich Pr...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Kaimann T,Metzger S,Kuhlmann K,Brandt B,Birkmann E,Höltje HD,Riesner D

    更新日期:2008-02-15 00:00:00

  • Characterization of the structure and the amyloidogenic properties of the Josephin domain of the polyglutamine-containing protein ataxin-3.

    abstract::Expansion of the polyglutamine (polyQ) region in the protein ataxin-3 is associated with spinocerebellar ataxia type 3, an inherited neurodegenerative disorder that belongs to the family of polyQ diseases. Increasing evidence indicates that protein aggregation and fibre formation play an important role in these pathol...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Masino L,Nicastro G,Menon RP,Dal Piaz F,Calder L,Pastore A

    更新日期:2004-12-03 00:00:00

  • Crystal structure analysis of free and substrate-bound 6-hydroxy-L-nicotine oxidase from Arthrobacter nicotinovorans.

    abstract::The pathway for oxidative degradation of nicotine in Arthrobacter nicotinovorans includes two genetically and structurally unrelated flavoenzymes, 6-hydroxy-L-nicotine oxidase (6HLNO) and 6-hydroxy-D-nicotine oxidase, which act with absolute stereospecificity on the L- and D-forms, respectively, of 6-hydroxy-nicotine....

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Kachalova GS,Bourenkov GP,Mengesdorf T,Schenk S,Maun HR,Burghammer M,Riekel C,Decker K,Bartunik HD

    更新日期:2010-02-26 00:00:00

  • The central PPT of the yeast retrotransposon Ty1 is not essential for transposition.

    abstract::The yeast retrotransposon Ty1 has structural and functional similarities to retroviruses. We report here that, as in retroviruses, the plus-strand DNA of Ty1 is synthesized as two segments. A central DNA flap is formed during reverse transcription consecutive to elongation (with strand displacement) of the upstream se...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Heyman T,Wilhelm M,Wilhelm FX

    更新日期:2003-08-08 00:00:00

  • Regulatory sequences in sigma 54 localise near the start of DNA melting.

    abstract::Transcription initiation by the enhancer-dependent sigma(54) RNA polymerase holoenzyme is positively regulated after promoter binding. The promoter DNA melting process is subject to activation by an enhancer-bound activator protein with nucleoside triphosphate hydrolysis activity. Tethered iron chelate probes attached...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Wigneshweraraj SR,Chaney MK,Ishihama A,Buck M

    更新日期:2001-03-02 00:00:00

  • Activation of DNA binding by the monomeric form of the P1 replication initiator RepA by heat shock proteins DnaJ and DnaK.

    abstract::RepA protein of plasmid P1 binds to arrays of 19 bp repeat sequences (iterons) and mediates initiation of replication and its control. Escherichia coli heat shock proteins DnaJ and DnaK can stimulate iteron binding activity of RepA in an ATP-dependent fashion. It has been proposed that RepA binds to DNA as monomers an...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: DasGupta S,Mukhopadhyay G,Papp PP,Lewis MS,Chattoraj DK

    更新日期:1993-07-05 00:00:00