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














  • Analysis of the relationship between side-chain conformation and secondary structure in globular proteins.

    abstract::The relationship between the preferred side-chain dihedral angles and the secondary structure of a residue was examined. The structures of 61 proteins solved to a resolution of 2.0 A (1 A = 0.1 nm) or better were analysed using a relational database to store the information. The strongest feature observed was that the...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: McGregor MJ,Islam SA,Sternberg MJ

    更新日期:1987-11-20 00:00:00

  • Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope.

    abstract::The single mutation L30 K in the Hu-Yap65 WW domain increased the stability of the complex with the peptide GTPPPPYTVG (K(d)=40(+/-5) microM). Here we report the refined solution structure of this complex by NMR spectroscopy and further derived structure-activity relationships by using ligand peptide libraries with tr...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Pires JR,Taha-Nejad F,Toepert F,Ast T,Hoffmüller U,Schneider-Mergener J,Kühne R,Macias MJ,Oschkinat H

    更新日期:2001-12-14 00:00:00

  • Crystal structure of the soluble domain of the major anaerobically induced outer membrane protein (AniA) from pathogenic Neisseria: a new class of copper-containing nitrite reductases.

    abstract::The major anaerobically induced outer membrane protein (AniA) from pathogenic Neisseria gonorrhoeae is essential for cell growth under oxygen limiting conditions in the presence of nitrite and is protective against killing by human sera. A phylogenic analysis indicates that AniA is a member of a new class of copper-co...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Boulanger MJ,Murphy ME

    更新日期:2002-02-01 00:00:00

  • Stability of coliphage lambda DNA replication initiator, the lambda O protein.

    abstract::The initiator of coliphage lambda DNA replication, lambda O protein, may be detected among other 35S-labeled phage and bacterial proteins by a method based on immunoprecipitation. This method makes it possible to study lambda O proteolytic degradation in lambda plasmid-harboring or lambda phage-infected cells; it avoi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Wegrzyn G,Pawlowicz A,Taylor K

    更新日期:1992-08-05 00:00:00

  • Ribosomal protein L9: a structure determination by the combined use of X-ray crystallography and NMR spectroscopy.

    abstract::The structure of protein L9 from the Bacillus stearothernophilus ribosome has been determined at 2.5 A resolution by refinement against single crystal X-ray diffraction data with additional constraints provided by NMR data. This highly elongated protein consists of two domains separated by a nine-turn connecting helix...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Hoffman DW,Cameron CS,Davies C,White SW,Ramakrishnan V

    更新日期:1996-12-20 00:00:00

  • Engineered oligomerization state of OmpF protein through computational design decouples oligomer dissociation from unfolding.

    abstract::Biogenesis of β-barrel membrane proteins is a complex, multistep, and as yet incompletely characterized process. The bacterial porin family is perhaps the best-studied protein family among β-barrel membrane proteins that allows diffusion of small solutes across the bacterial outer membrane. In this study, we have iden...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Naveed H,Jimenez-Morales D,Tian J,Pasupuleti V,Kenney LJ,Liang J

    更新日期:2012-05-25 00:00:00

  • Unusual Cys-Tyr covalent bond in a large catalase.

    abstract::Catalase-1, one of four catalase activities of Neurospora crassa, is associated with non-growing cells and accumulates in asexual spores. It is a large, tetrameric, highly efficient, and durable enzyme that is active even at molar concentrations of hydrogen peroxide. Catalase-1 is oxidized at the heme by singlet oxyge...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Díaz A,Horjales E,Rudiño-Piñera E,Arreola R,Hansberg W

    更新日期:2004-09-17 00:00:00

  • A highly conserved lysine residue in phi29 DNA polymerase is important for correct binding of the templating nucleotide during initiation of phi29 DNA replication.

    abstract::DNA polymerases that initiate replication by protein-priming are able to catalyze terminal protein (TP)-primed initiation, the following transition steps and finally DNA-primed elongation. Therefore, their structures must be able to position sequentially both primers, TP and DNA, at a common binding site. For DNA-temp...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Truniger V,Lázaro JM,Blanco L,Salas M

    更新日期:2002-04-19 00:00:00

  • An additional dimer linkage structure in Moloney murine leukemia virus RNA.

    abstract::We have identified an additional dimerization linkage structure in the genome of Moloney murine leukemia virus (MoMLV). Retroviral genomes have long been known to be linked at their 5' ends to form dimers. In MoMLV, a hairpin loop functioning as a dimer linkage structure (DLS) has previously been identified at nucleot...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Oroudjev EM,Kang PC,Kohlstaedt LA

    更新日期:1999-08-20 00:00:00

  • Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin.

    abstract::Membranes have a potent ability to promote secondary structure formation in a wide range of membrane-active peptides, believed to be due to a reduction through hydrogen bonding of the energetic cost of partitioning peptide bonds. This process is of fundamental importance for understanding the mechanism of action of to...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Ladokhin AS,White SH

    更新日期:1999-01-29 00:00:00

  • Kinetic stability and crystal structure of the viral capsid protein SHP.

    abstract::SHP, the capsid-stabilizing protein of lambdoid phage 21, is highly resistant against denaturant-induced unfolding. We demonstrate that this high functional stability of SHP is due to a high kinetic stability with a half-life for unfolding of 25 days at zero denaturant, while the thermodynamic stability is not unusual...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Forrer P,Chang C,Ott D,Wlodawer A,Plückthun A

    更新日期:2004-11-12 00:00:00

  • Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta.

    abstract::The nuclear receptors peroxisome proliferator-activated receptors (PPARs) are known for their critical role in the metabolic syndrome. Here, we show that they are direct regulators of the family of pyruvate dehydrogenase kinase (PDK) genes, whose products act as metabolic homeostats in sensing hunger and satiety level...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Degenhardt T,Saramäki A,Malinen M,Rieck M,Väisänen S,Huotari A,Herzig KH,Müller R,Carlberg C

    更新日期:2007-09-14 00:00:00

  • Experimental and theoretical studies of the effects of deoxyribose substitutions on the stability of the UUCG tetraloop.

    abstract::Experimental and theoretical thermodynamic studies of the consequences of 2'-hydroxyl substitution in the RNA UUCG tetraloop show distinct position dependence consistent with the diverse structural contexts of the four-loop ribose hydroxyls in this motif. The results suggest that even for simple substitutions, such as...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Williams DJ,Hall KB

    更新日期:2000-03-17 00:00:00

  • Eliminating the requirement of an essential gene product in an already very small virus: scaffolding protein B-free øX174, B-free.

    abstract::Unlike most viral assembly systems, two scaffolding proteins, B and D, mediate bacteriophage øX174 morphogenesis. The external scaffolding protein D is highly ordered in the atomic structure and proper function is very sensitive to mutation. In contrast, the internal scaffolding protein B is relatively unordered and e...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Chen M,Uchiyama A,Fane BA

    更新日期:2007-10-19 00:00:00

  • The binding of 2-deoxy-D-glucose 6-phosphate to glycogen phosphorylase b: kinetic and crystallographic studies.

    abstract::Kinetic and crystallographic studies have characterized the effect of 2-deoxy-glucose 6-phosphate on the catalytic and structural properties of glycogen phosphorylase b. Previous work on the binding of glucose 6-phosphate, a potent physiological inhibitor of the enzyme, to T state phosphorylase b in the crystal showed...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Oikonomakos NG,Zographos SE,Johnson LN,Papageorgiou AC,Acharya KR

    更新日期:1995-12-15 00:00:00

  • Solution Conformation of Bovine Leukemia Virus Gag Suggests an Elongated Structure.

    abstract::Bovine leukemia virus (BLV) is a deltaretrovirus that infects domestic cattle. The structural protein Gag, found in all retroviruses, is a polyprotein comprising three major functional domains: matrix (MA), capsid (CA), and nucleocapsid (NC). Previous studies have shown that both mature BLV MA and NC are able to bind ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Qualley DF,Cooper SE,Ross JL,Olson ED,Cantara WA,Musier-Forsyth K

    更新日期:2019-03-15 00:00:00

  • Nucleotide binding to DNA gyrase causes loss of DNA wrap.

    abstract::DNA gyrase negatively supercoils DNA in a reaction coupled to the binding and hydrolysis of ATP. Limited supercoiling can be achieved in the presence of the non-hydrolysable ATP analogue, 5'-adenylyl beta,gamma-imidodiphosphate (ADPNP). In order to negatively supercoil DNA, gyrase must wrap a length of DNA around itse...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Heddle JG,Mitelheiser S,Maxwell A,Thomson NH

    更新日期:2004-03-26 00:00:00

  • Structural insight into how an anti-idiotypic antibody against D3H44 (anti-tissue factor antibody) restores normal coagulation.

    abstract::6A6 is a murine monoclonal antibody raised against the humanized anti-tissue factor antibody D3H44. 6A6 is able to completely neutralize the anticoagulant activity of D3H44 in tissue factor-dependent functional assays, such as endotoxin-induced whole blood clotting, prothrombin time, as well as factor X and factor IX ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Eigenbrot C,Meng YG,Krishnamurthy R,Lipari MT,Presta L,Devaux B,Wong T,Moran P,Bullens S,Kirchhofer D

    更新日期:2003-08-08 00:00:00

  • Calculations of electrostatic energies in proteins. The energetics of ionized groups in bovine pancreatic trypsin inhibitor.

    abstract::The importance of including different energy contributions in calculations of electrostatic energies in proteins is examined by calculating the intrinsic pKa values of the acidic groups of bovine pancreatic trypsin inhibitor. It appears that such calculations provide a powerful and revealing test; the relevant solvati...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Russell ST,Warshel A

    更新日期:1985-09-20 00:00:00

  • Translocation of histone proteins across lipid bilayers and Mycoplasma membranes.

    abstract::We show that the three core histones H2A, H3 and H4 can transverse lipid bilayers of large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In contrast, the histone H2B, although able to bind to the liposomes, fails to penetrate the unilamellar and the multilamellar vesicles. Translocation across the lip...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Rosenbluh J,Hariton-Gazal E,Dagan A,Rottem S,Graessmann A,Loyter A

    更新日期:2005-01-14 00:00:00

  • Regulation of Shigella Effector Kinase OspG through Modulation of Its Dynamic Properties.

    abstract::Gram-negative pathogens secrete effector proteins into human cells to modulate normal cellular processes and establish a bacterial replication niche. Shigella and pathogenic Escherichia coli possess homologous effector kinases, OspG and NleH1/2, respectively. Upon translocation, OspG but not NleH binds to ubiquitin an...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Grishin AM,Barber KR,Gu RX,Tieleman DP,Shaw GS,Cygler M

    更新日期:2018-07-06 00:00:00

  • The presequence of fumarase is exposed to the cytosol during import into mitochondria.

    abstract::The majority of mitochondrial proteins can be imported into mitochondria following termination of their translation in the cytosol. Import of fumarase and several other proteins into mitochondria does not appear to occur post-translationally according to standard in vivo and in vitro assays. However, the nature of int...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Karniely S,Regev-Rudzki N,Pines O

    更新日期:2006-04-28 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


    authors: Rosendahl G,Douthwaite S

    更新日期:1993-12-20 00:00:00

  • Domain closure in lactoferrin. Two hinges produce a see-saw motion between alternative close-packed interfaces.

    abstract::Lactoferrin is an iron transport protein. Upon binding iron, the two domains in the N-terminal half of the molecule move together. Previous work has shown that this domain closure involves two hinges. Using the newly refined structure of the open form, the structural mechanism underlying this motion is analyzed here i...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Gerstein M,Anderson BF,Norris GE,Baker EN,Lesk AM,Chothia C

    更新日期:1993-11-20 00:00:00

  • Adrm1, a putative cell adhesion regulating protein, is a novel proteasome-associated factor.

    abstract::We have identified Adrm1 as a novel component of the regulatory ATPase complex of the 26 S proteasome: Adrm1 was precipitated with an antibody to proteasomes and vice versa. Adrm1 co-migrated with proteasomes on gel-filtration chromatography and non-denaturing polyacrylamide gel electrophoresis. Adrm1 has been describ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Jørgensen JP,Lauridsen AM,Kristensen P,Dissing K,Johnsen AH,Hendil KB,Hartmann-Petersen R

    更新日期:2006-07-28 00:00:00

  • RNA-DNA hybrid formation at a bacteriophage T4 replication origin.

    abstract::The bacteriophage T4 replication origins ori(uvsY) and ori(34) each contain two distinct components: a T4 middle-mode promoter that is strictly required for replication and a downstream region of about 50 bp that is required for maximal levels of replication. Here, we present evidence that structure of the downstream ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Carles-Kinch K,Kreuzer KN

    更新日期:1997-03-14 00:00:00

  • In crystallo capture of a Michaelis complex and product-binding modes of a bacterial phosphotriesterase.

    abstract::The mechanism by which the binuclear metallophosphotriesterases (PTEs, E.C. catalyse substrate hydrolysis has been extensively studied. The mu-hydroxo bridge between the metal ions has been proposed to be the initiating nucleophile in the hydrolytic reaction. In contrast, analysis of some biomimetic systems h...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Jackson CJ,Foo JL,Kim HK,Carr PD,Liu JW,Salem G,Ollis DL

    更新日期:2008-02-01 00:00:00

  • Bacteriophage p22 portal vertex formation in vivo.

    abstract::Bacteriophage with double-stranded, linear DNA genomes package DNA into pre-assembled icosahedral procapsids through a unique vertex. The packaging vertex contains an oligomeric ring of a portal protein that serves as a recognition site for the packaging enzymes, a conduit for DNA translocation, and the site of tail a...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Moore SD,Prevelige PE Jr

    更新日期:2002-02-01 00:00:00

  • Structure of the connector of bacteriophage T7 at 8A resolution: structural homologies of a basic component of a DNA translocating machinery.

    abstract::The three-dimensional structure of the bacteriophage T7 head-to-tail connector has been obtained at 8A resolution using cryo-electron microscopy and single-particle analysis from purified recombinant connectors. The general morphology of the T7 connector is that of a 12-folded toroidal homopolymer with a channel that ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Agirrezabala X,Martín-Benito J,Valle M,González JM,Valencia A,Valpuesta JM,Carrascosa JL

    更新日期:2005-04-15 00:00:00

  • Efficient recovery of high-affinity antibodies from a single-chain Fab yeast display library.

    abstract::Yeast display is a powerful technology for the isolation of monoclonal antibodies (mAbs) against a target antigen. Antibody libraries have been displayed on the surface of yeast as both single-chain variable fragment (scFv) and antigen binding fragment (Fab). Here, we combine these two formats to display well-characte...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章


    authors: Walker LM,Bowley DR,Burton DR

    更新日期:2009-06-05 00:00:00