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G Jun

Publications and source records attributed to G Jun.

10 recordsLinked to original sources

Deciphering the design of the tropomyosin molecule.

The crystal structure at 2.0-A resolution of an 81-residue N-terminal fragment of muscle alpha-tropomyosin reveals a parallel two-stranded alpha-helical coiled-coil structure with a remarkable core. The high alanine content of the molecule is clustered into short regions where the local 2-fold symmetry is broken by a small (approximately 1.2-A) axial staggering of the helices. The joining of these regions with neighboring segments, where the helices are in axial register, gives rise to specific bends in the molecular axis. We observe such bends to be widely distributed in two-stranded alpha-helical coiled-coil proteins. This asymmetric design in a dimer of identical (or highly similar) sequences allows the tropomyosin molecule to adopt multiple bent conformations. The seven alanine clusters in the core of the complete molecule (which spans seven monomers of the actin helix) promote the semiflexible winding of the tropomyosin filament necessary for its regulatory role in muscle contraction.

Alanine↗

The crystal structure of modified bovine fibrinogen.

Here we report the crystal structure at approximately 4-A resolution of a selectively proteolyzed bovine fibrinogen. This key component in hemostasis is an elongated 340-kDa glycoprotein in the plasma that upon activation by thrombin self-assembles to form the fibrin clot. The crystals are unusual because they are made up of end-to-end bonded molecules that form flexible filaments. We have visualized the entire coiled-coil region of the molecule, which has a planar sigmoidal shape. The primary polymerization receptor pockets at the ends of the molecule face the same way throughout the end-to-end bonded filaments, and based on this conformation, we have developed an improved model of the two-stranded protofibril that is the basic building block in fibrin. Near the middle of the coiled-coil region, the plasmin-sensitive segment is a hinge about which the molecule adopts different conformations. This segment also includes the boundary between the three- and four-stranded portions of the coiled coil, indicating the location on the backbone that anchors the extended flexible Aalpha arm. We suggest that a flexible branch point in the molecule may help accommodate variability in the structure of the fibrin clot.

Animals↗

Promoter trapping identifies real genes in C. elegans.

Promoter trapping involved screening uncharacterized fragments of C. elegans genomic DNA for C. elegans promoter activity. By sequencing the ends of these DNA fragments and locating their genomic origin using the available genome sequence data, promoter trapping has now been shown to identify real promoters of real genes, exactly as anticipated. Developmental expression patterns have thereby been linked to gene sequence, allowing further inferences on gene function to be drawn. Some expression patterns generated by promoter trapping include subcellular details. Localization to the surface of particular cells or even particular aspects of the cell surface was found to be consistent with the genes, now associated with these patterns, encoding membrane-spanning proteins. Data on gene expression patterns are easier to generate and characterize than mutant phenotypes and may provide the best means of interpreting the large quantity of sequence data currently being generated in genome projects.

Animals↗

Interactions of nucleotides with fully unadenylylated glutamine synthetase from Salmonella typhimurium.

Glutamine synthetase (GS) catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia in the presence of divalent cations. To gain insight into the structural basis of the feedback inhibition of GS by AMP, we have studied crystal structures of GS complexes with AMP and the related molecules: AMPPNP (a less hydrolyzable ATP analog), ADP, GDP, adenosine, and adenine. AMP is a feedback inhibitor of GS; ATP and ADP are cofactors, and AMPPNP, GDP, adenosine, and adenine are also GS inhibitors. GS used in this study is from Salmonella typhimurium and is free of covalent modification by adenylylation. All of the crystals examined contain two bound MN2+ ions per GS subunit. The X-ray structures show that all nucleotides bind at the same site, the cofactor ATP binding site, as do adenosine and adenine. Thus from X-ray structures, AMP, adenosine, adenine, and GDP would be expected to inhibit GS-Mn by competing with the substrate ATP for the active site. This suggestion from the crystal structures that AMP is competitive with respect to ATP is supported by kinetic measurements using the biosynthetic assay.

Adenine↗

Mapping of an epitope defined by a human hybridoma antibody (TrD3): a new HLA-B supertype associated with a subset of HLA-Bw6.

The new human-human hybridoma TrD3 secretes a cytotoxic IgM mAb, which reacted with 28 of a panel of 56 HLA-typed lymphoblastoid cells. All 28 TrD3+ cells expressed the HLA-B supertype Bw6, whereas 10 Bw6+ cells were not recognized by the mAb. None of the 17 Bw4 homozygous cells were positive with TrD3. Thus, TrD3 divided the Bw6+ HLA-B specificities of the cell lines into two subgroups, namely, Bw6+TrD3+ and Bw6+TrD3-, and therefore defines a new HLA-B supertype. TrD3 reacted strongly with some B8+ cell lines and weakly or not at all with others, suggesting a new split of HLA-B8. Compared with cell lines, TrD3 reacted more weakly with freshly isolated T cells from blood. The Bw6-specific rat mAb SFR8-B6 partially blocked the binding of 125I-labeled TrD3 to a Bw6+ cell line. By using cell lines transfected with hybrid genes between HLA-B7 (Bw6+) and HLA-B27 (Bw6-) as targets in flow cytometry, critical residues for the TrD3 epitope could be mapped to the amino acid region 24-62 of the HLA class-I alpha 1 domain. Comparison of deduced amino acid sequences of TrD3-positive and -negative cells indicated that a tryptophane residue at position 95 destroyed the TrD3 epitope, and that one or more of the residues in positions 24, 45, and 46 may be critical, suggesting that it is a discontinuous epitope. It is notable that none of these residues are located on alpha-helixes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[Report of experience with a socio- and psychotherapeutically oriented open long-term group of parents of severerly brain injured children treated in an outpatient clinic].

In 1972, we started a discussion group for parents of children with severe brain damage. The emerging group dynamic was dialectically determined, on the one hand, by the heterogeneity of the parents' different personalities and reactions to their experience and, on the other, by the homogeneity of the problem to be borne and solved in common: the handicapped child in family and society.

Adult↗