Biomedical subjects

J Meiler

Publications and source records attributed to J Meiler.

At least 19 recordsLinked to original sources

PubMed2001

Determination of aliphatic side-chain conformation using cross-correlated relaxation: application to an extraordinarily stable 2'-aminoethoxy-modified oligonucleotide triplex.

The structural basis for the extraordinary stability of a triple-stranded oligonucleotide in which the third strand contains 2'-aminoethoxy-substituted riboses is investigated by NMR spectroscopy. The enhanced stability of the modified triplex in comparison to the unmodified DNA triplex of the same sequence can be attributed to strong interactions of the aminoethoxy groups of the third strand with the phosphate groups of the purine strand. In molecular dynamics calculations the aminoethoxy side chain was found to be rather flexible, allowing for the presence of hydrogen bonds between the aminoethoxy group of the third strand and two different phosphates of the backbone of the second strand. To investigate the conformational preference of the aminoethoxy side chain a new NMR method has been developed which relies on CH-CH dipolar-dipolar cross-correlated relaxation rates. The results indicate that the aminoethoxy side chains adopt mainly a gauche(+) conformation, for which only one of the two hydrogen bonds inferred by NMR and molecular dynamics simulations is possible. This demonstrates a highly specific interaction between the amino group of the third strand and one of the phosphate groups of the purine strand.

Base Sequence↗

PubMed2001

Model-free approach to the dynamic interpretation of residual dipolar couplings in globular proteins.

The effects of internal motions on residual dipolar NMR couplings of proteins partially aligned in a liquid-crystalline environment are analyzed using a 10 ns molecular dynamics (MD) computer simulation of ubiquitin. For a set of alignment tensors with different orientations and rhombicities, MD-averaged dipolar couplings are determined and subsequently interpreted for different scenarios in terms of effective alignment tensors, average orientations of dipolar vectors, and intramolecular reorientational vector distributions. Analytical relationships are derived that reflect similarities and differences between motional scaling of dipolar couplings and scaling of dipolar relaxation data (NMR order parameters). Application of the self-consistent procedure presented here to dipolar coupling measurements of biomolecules aligned in different liquid-crystalline media should allow one to extract in a "model-free" way average orientations of dipolar vectors and specific aspects of their motions.

Computer Simulation↗

PubMed2001

Tip60 is a cell-type-specific transcriptional regulator.

Tip60 was originally identified as cellular HIV-Tat interacting protein and has been shown to augment Tat-dependent transcription. It has also been shown to interact with various cellular transcription factors and to belong to the nuclear histone acetyltransferase (HAT) family. To further elucidate the function of Tip60 and its HAT domain in transcription regulation, we compared Tip60 activity in HeLa and Jurkat T lymphoma cells. Here we show that Tip60 augments the HIV-1 Tat activity at the HIV-LTR promoter in HeLa but inhibits it in Jurkat cells. Moreover, we isolated two new variants of the Tip60 protein (Tip60Delta1, Tip60Delta2) from Jurkat cells. The Tip60Delta2 variant lacks the entire HAT domain but modulates HIV-1 Tat activity like full-length Tip60. In addition, Tip60 and the transcriptional repressor ZEB (zinc finger E box binding protein) interact specifically in the yeast two-hybrid system and additively inhibit the CD4 enhancer/promoter activity in Jurkat cells. Thus, Tip60 may function as corepressor of the ZEB protein. In summary, these data show that Tip60 functions as a cell-type-specific transcriptional regulator and that the HAT domain is not required for either transcriptional activation or inhibition. This indicates that Tip60 may function by recruiting additional cell-type-specific cofactors.

Acetyltransferases↗

PubMed2000

DipoCoup: A versatile program for 3D-structure homology comparison based on residual dipolar couplings and pseudocontact shifts.

A program, DipoCoup, is presented that allows to search the protein data bank for proteins which have a three dimensional fold that is at least partially homologous to a protein under investigation. The three dimensional homology search uses secondary structure alignment based on chemical shifts and dipolar couplings or pseudocontact shifts for the three dimensional orientation of secondary structure elements. Moreover, the program offers additional tools for handling and analyzing dipolar couplings.

Amino Acid Sequence↗

PubMed2000

A new approach for applying residual dipolar couplings as restraints in structure elucidation.

Residual dipolar couplings are useful global structural restraints. The dipolar couplings define the orientation of a vector with respect to the alignment tensor. Although the size of the alignment tensor can be derived from the distribution of the experimental dipolar couplings, its orientation with respect to the coordinate system of the molecule is unknown at the beginning of structure determination. This causes convergence problems in the simulated annealing process. We therefore propose a protocol that translates dipolar couplings into intervector projection angles, which are independent of the orientation of the alignment tensor with respect to the molecule. These restraints can be used during the whole simulated annealing protocol.

Amino Acids↗

PubMed1999

Negative regulation of CD4 expression in T cells by the transcriptional repressor ZEB.

ZEB, an E-box binding transcriptional repressor, is an important regulator of T cell and muscle development. Targeted disruption of ZEB in mice resulted in a strong reduction of thymocytes and the few T cells that reached the mature stage were predominantly CD4(+). CD4 expression during the various stages of T cell differentiation is controlled at the transcriptional level by a complex array of regulatory elements in the CD4 gene locus, consisting of at least three enhancers, one promoter and one silencer. Here we present evidence that CD4 gene expression is negatively regulated by ZEB. We show that ZEB binds to the 5'E-box in the CD4-3 element of the proximal CD4 enhancer in competition with the transcriptional activators E12 and HEB, thereby reducing CD4 expression on CD4 single-positive but not CD4/CD8 double-positive T cells. The conversion of the CD4 proximal enhancer into a potential silencer element by the transcriptional repressor ZEB offers an additional concept of CD4 gene regulation in T cells.

Animals↗

PubMed1992

[Factors influencing radiation exposure in radiography].

After explaining how to correct total prefiltration of an x-ray-tube assembly, and of the factors influencing radiation exposure when taking x-rays, the article shows how at a known voltage radiation exposure is determined from the mAs values. Comparative radiation exposure values are given for various types of prefiltration.

Humans↗

PubMed1989

[Simplified determination of the effective prefiltration of an X-ray tube].

For determining the effective prefiltration of an x-ray tube assembly only a very expensive method was known up to now that is not suitable for a general use. Therefore, no reliable data for prefiltration could be stated in individual cases. The present article describes a method useful for determination of the prefiltration. With this method reliable statements on the radiation exposure of the patient are possible in every case.

Filtration↗

PubMed1989