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Biomedical subjects

J M Berg

Publications and source records attributed to J M Berg.

At least 73 records · Page 4Linked to original sources
PubMed1991

A family with multiple instances of definite, probable and possible early-onset Alzheimer's disease.

A family with a multigenerational history of proven or suspected early-onset Alzheimer's disease (AD) consistent with autosomal-dominant inheritance is described. To date, the pedigree comprises five generations in which there are 13 known affected individuals. The mean age of onset of cognitive deficits in those for whom data are available (n = 11) is 47.6 (s.d. 3.0) years and the mean age of death (n = 10) is 58.8 (s.d. 4.0) years. The variability in the extent and quality of available data illustrates the diagnostic difficulties encountered in ascertaining such an extended pedigree, and the need for caution in interpreting the evidence.

Adult↗
PubMed1990

Retroviral nucleocapsid protein-metal ion interactions: folding and sequence variants.

Retroviral nucleocapsid proteins contain one or two proposed metal-binding sequences of the form Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys. Previously, we reported that an 18-amino acid peptide derived from the nucleocapsid protein of Rauscher murine leukemia virus (RMLV) binds metals such as Co2+ and Zn2+. We have now synthesized the entire nucleocapsid protein from RMLV. We report here that the protein also binds Co2+ and Zn2+ and does so with a higher affinity than does the peptide. Limited proteolysis and circular dichroism studies reveal that metal binding induces folding of the metal-binding domain and, perhaps, the regions adjacent to it but the remainder of the protein remains in a relatively unstructured state. In addition, we have synthesized sequence variants of the metal-binding domain that correspond to viral mutations reported in the literature. In many cases, the metal-binding properties of these peptides correlate with the observed biological activity, providing further evidence for the importance of metal binding to nucleocapsid function.

Amino Acid Sequence↗
PubMed1990

Zinc finger domains: hypotheses and current knowledge.

Many of the hypotheses are clearly correct that are based on the initial observation that TFIIIA has an approximately periodic structure with invariant pairs of cysteines and histidines apparently capable of coordinating metal ions. A startling number of other cDNA clones encode proteins that contain one or more sequences that match the zinc finger consensus, revealing that zinc finger proteins represent perhaps the largest class of DNA binding proteins in eukaryotes and that zinc finger protein-controlled gene expression may be a fundamental aspect of development as well as other processes. A great deal of progress has been made in elucidating the structure of single zinc finger domains. From knowledge of these structures, plausible and testable models can be developed for the complexes between zinc finger proteins and their DNA binding sites. Clearly, one of the most important challenges remaining in this area involves testing and extending these models. Structural data on such protein-nucleic acid complexes derived from NMR or crystallographic studies is tremendously valuable in this regard. Finally, an additional fundamental question is raised by the observation that this family and other important nucleic acid binding proteins contain zinc ions bound in small structural domains. Is zinc binding merely a useful structural strategy for generating domains involved in macromolecular interactions, or are zinc concentration fluctuations used in some manner to regulate gene expression? The biophysical data available to date certainly do not rule out this intriguing possibility.

Amino Acid Sequence↗
PubMed1989

A retroviral Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys peptide binds metal ions: spectroscopic studies and a proposed three-dimensional structure.

Retroviral gag gene-encoded core nucleic acid binding proteins contain either one or two sequences of the form Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys. Previously, one of us has proposed that these sequences form metal-binding domains in analogy with the "zinc finger" domains first observed in transcription factor IIIA. We report that an 18-amino acid peptide derived from the core nucleic acid binding protein from Rauscher murine leukemia virus binds metal ions such as Co2+ and Zn2+. The absorption spectrum of the peptide-Co2+ complex is highly suggestive of tetrahedral coordination involving three cysteinates and one histidine. Titration experiments indicate that the dissociation constant for the peptide-Co2+ complex is 1.0 microM and that Zn2+ binds more tightly than Co2+. A detailed three-dimensional structure for this domain based on conserved substructures in other crystallographically characterized metalloproteins and on a detailed analysis of the Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys sequences from retroviruses and other related sources is proposed.

Amino Acid Sequence↗
PubMed1988

Decreased platelet 3H-imipramine binding in Down's syndrome.

Platelet 3H-imipramine binding in 12 subjects with Down's syndrome showed a significantly lower maximal number of binding sites (Bmax) as compared to both unrelated normal and parental controls. No difference in the affinity constant (Kd) was observed. The results support the value of the platelet 3H-imipramine binding assay in the investigation of defects in serotonin metabolism in humans.

Adolescent↗
PubMed1988

Proposed structure for the zinc-binding domains from transcription factor IIIA and related proteins.

Several proteins, including the gene regulatory protein transcription factor IIIA, have been shown to contain tandem repeats of sequences of approximately equal to 30 amino acids that are believed to form structural domains around bound zinc ions ("zinc fingers"). The consensus sequence for these repeats is (Phe, Tyr)-Xaa-Cys-(Xaa)2 or 4-Cys-(Xaa)3-Phe-(Xaa)5-Leu-(Xaa)2-His-(Xaa)3-His- (Xaa)5, where Xaa is any amino acid. Comparisons with metalloproteins with known structures have allowed the development of a detailed three-dimensional model for these domains consisting of an antiparallel beta-sheet followed by an alpha-helix. The proposed structure provides a basis for understanding the detailed roles of the conserved residues and allows construction of a model for the interaction of these proteins with nucleic acids in which the proteins wrap around the nucleic acids in the major groove.

Amino Acid Sequence↗
PubMed1988

Twenty-six years later: a woman with tetra-X chromosomes.

A 26-year follow-up of the first reported female with tetra-X chromosomes is presented. Mental and physical manifestations, and their variability, are considered with reference to this woman and other documented examples of the uncommon chromosomal aberration concerned.

Adult↗
PubMed1987

Metal-dependent folding of a single zinc finger from transcription factor IIIA.

A 30-amino acid peptide, which corresponds to the second "zinc finger" domain of transcription factor IIIA, has been synthesized and purified. This peptide folds in the presence of zinc: adding Zn2+ significantly changes the circular dichroism spectrum, and Zn2+ protects the peptide from tryptic digestion. The peptide also binds Co2+, and the absorption spectrum of the Co2+ complex suggests that a tetrahedral binding site is formed by two cysteines and two histidines. Experiments at higher temperatures (60-75 degrees C) suggest that these folded metal-peptide complexes are quite thermostable. The peptide shows some sequence-specific effects in DNase and methylation protection experiments. However, it does not give a clear "footprint," and some effects are observed in the absence of added zinc.

Amino Acid Sequence↗
PubMed1986

Potential metal-binding domains in nucleic acid binding proteins.

A systematic search for sequences that potentially could form metal-binding domains in proteins has been performed. Five classes of proteins involved in nucleic acid binding or gene regulation were found to contain such sequences. These observations suggest numerous experiments aimed at determining whether metal-binding domains are present in these proteins and, if present, what roles such domains play in the processes of nucleic acid binding and gene regulation.

Adenoviridae↗
PubMed1986

Prenatal diagnosis of mental retardation and its implications.

Prenatal diagnostic procedures and their implications are reviewed with particular reference to mental retardation. The subject has biomedical, psychosocial, ethical, and legal ramifications, and consideration is given to each of these. These issues require the attention of psychiatrists because of emotional stresses, anxieties, and conflicts engendered by the circumstances under which consideration of prenatal diagnostic procedures becomes relevant, by the undertakings themselves, and by the complex and sensitive decisions that may subsequently need to be made.

Female↗
PubMed1985

Systematic variation in DNA length yields highly ordered repressor-operator cocrystals.

Crystals have been grown that contain the operator-binding domain of the lambda repressor and the lambda operator site OL1. Crystallization conditions were tested with a set of DNA fragments, ranging in length from 17 to 23 base pairs. The best crystals were grown with a 20-base pair DNA fragment. These crystals have space-group symmetry P2I, with unit cell dimensions a = 37.1 A, b = 68.8 A, c = 56.8 A, and a beta angle of 91.5 degrees. They diffracted to at least 2.5 A resolution. High resolution data from these crystals should allow the direct determination of how a repressor recognizes its operator site.

Base Sequence↗
PubMed1981

The puppet-like syndrome of Angelman.

Five new cases are presented of a syndrome characterized mainly by severe mental retardation, epilepsy, puppet-like ataxic movements, microbrachycephaly, prognathism, tongue protrusion, and inappropriate paroxysms of laughter. The cases are analyzed with reference to personal and family histories, clinical findings, and results of special investigations (biochemical, chromosomal, dermatoglyphic, EEG, and radiologic). The findings are compared with those in the 22 patients described previously. Though clinically distinctive, there is as yet no clear-cut evidence as to cause.

Adolescent↗