Biomedical subjects

Claudio Anselmi

Publications and source records attributed to Claudio Anselmi.

11 recordsLinked to original sources

PubMed2007

Origin of functional diversity among tetrameric voltage-gated channels.

The aim of the present work is to relate functional differences of voltage-gated K(+) (K(v)), hyperpolarization-activated cyclic nucleotide-gated (HCN), and cyclic nucleotide gated (CNG) channels to differences in their amino acid sequences. By means of combined bioinformatic sequence analyses and homology modelling, we suggest that: (1) CNG channels are less voltage-dependent than K(v) channels since the charge of their voltage sensor, the S4 helix, is lower than that of K(v) channels and because of the presence of a conserved proline in the S4-S5 linker, which is quite likely to uncouple S4 from S5 and S6. (2) In HCN channels, S4 features a higher net positive charge with respect to K(v) channels and an extensive network of hydrophobic residues, which is quite likely to provide a tight coupling among S4 and the neighboring helices. We suggest insights on the gating of HCN channels and the reasons why they open with membrane hyperpolarization and with a significantly longer time constant with respect to other channels.

Amino Acid Motifs↗

PubMed2006

Ligand specificity of odorant receptors.

Odorant receptors belong to class A of the G protein-coupled receptors (GPCRs) and detect a large number of structurally diverse odorant molecules. A recent structural bioinformatic analysis suggests that structural features are conserved across class A of GPCRs in spite of their low sequence identity. Based on this work, we have aligned the sequences of 29 ORs for which ligand binding data are available. Recent site-directed mutagenesis experiments on one such receptor (MOR174-9) provide information that helped to identify nine amino-acid residues involved in ligand binding. Our modeling provides a rationale for amino acids in equivalent positions in most of the odorant receptors considered and helps to identify other amino acids that could be important for ligand binding. Our findings are consistent with most of the previous models and allow predictions for site-directed mutagenesis experiments, which could also validate our model.

Amino Acid Sequence↗

PubMed2005

Coarse-grained model of proteins incorporating atomistic detail of the active site.

We present a novel approach to explore the conformational space of globular proteins near their native state. It combines the advantages of coarse-grained models with those of all-atoms simulations, required to treat molecular recognition processes. The comparison between calculated structural properties with those obtained with all-atoms molecular dynamics simulations establishes the accuracy of the model. Our method has the potential to be extended to molecular recognition processes in systems whose characteristic size and time scale prevent an analysis based on all-atoms molecular dynamics.

Amyloid Precursor Protein Secretases↗

PubMed2005

Nanoscale mechanical and dynamical properties of DNA single molecules.

Experimental evidence suggests DNA mechanical properties, in particular intrinsic curvature and flexibility, have a role in many relevant biological processes. Systematic investigations about the origin of DNA curvature and flexibility have been carried out; however, most of the applied experimental techniques need simplifying models to interpret the data, which can affect the results. Progress in the direct visualization of macromolecules allows the analysis of morphological properties and structural changes of DNAs directly from the digitised micrographs of single molecules. In addition, the statistical analysis of a large number of molecules gives information both on the local intrinsic curvature and the flexibility of DNA tracts at nanometric scale in relatively long sequences. However, it is necessary to extend the classical worm-like chain model (WLC) for describing conformations of intrinsically straight homogeneous polymers to DNA. This review describes the various methodologies proposed by different authors.

Cations, Divalent↗

PubMed2005

Theoretical models of possible compact nucleosome structures.

Chromatin structure seems related to the DNA linker length. This paper presents a systematic search of the possible chromatin structure as a function of the linker lengths, starting from three different low-resolution molecular models of the nucleosome. Gay-Berne potential was used to evaluate the relative nucleosome packing energy. Results suggest that linker DNAs, which bridges and orientate nucleosomes, affect both the geometry and the rigidity of the global chromatin structure.

DNA↗

PubMed2004

Organization of telomeric nucleosomes: atomic force microscopy imaging and theoretical modeling.

Telomeric chromatin has peculiar features with respect to bulk chromatin, which are not fully clarified to date. Nucleosomal arrays, reconstituted on fragments of human telomeric DNA and on tandemly repeated tetramers of 5S rDNA, have been investigated at single-molecule level by atomic force microscopy and Monte Carlo simulations. A satisfactory correlation emerges between experimental and theoretical internucleosomal distance distributions. However, in the case of telomeric nucleosomal arrays containing two nucleosomes, we found significant differences. Our results show that sequence features of DNA are significant in the basic chromatin organization, but are not the only determinant.

Animals↗

PubMed2004

Dual role of sequence-dependent DNA curvature in nucleosome stability: the critical test of highly bent Crithidia fasciculata DNA tract.

In spite of the knowledge of the nucleosome molecular structure, the role of DNA intrinsic curvature in determining nucleosome stabilization is still an open question. In this paper, we describe a general model that allows the prediction of the nucleosome stability, tested on 83 different DNA sequences, in surprising good agreement with the experimental data, carried out in ours as well as in many other laboratories. The model is based on the dual role of DNA curvature in nucleosome thermodynamic stabilization. A critical test is the evaluation of the nucleosome free energy relative to a Crithidia fasciculata kinetoplast DNA fragment, which represents the most curved DNA found so far in biological systems and, therefore, is generally believed to form a highly stable nucleosome.

Animals↗

PubMed2004

A possible role of DNA superstructures in genome evolution.

The concept of DNA as a simple repository of the gene information has changed in that of a polymorphic macromolecule, which plays a relevant part in the management of the complex biochemical transformations in living matter. As a consequence of the slight stereochemical differences between base pairs, the direction of the DNA double helix axis undergoes deterministic writhing. A useful representation of such sequence-dependent structural distortions is the curvature diagram. Here, it is reported as an evolution simulation obtained by extensive point mutations along a biologically important DNA tract. The curvature changes, consequence of the point mutations. were compared to the related experimental gel electrophoresis mobility. The curvature of most mutants decreases and the mobility increases accordingly, suggesting the curvature of that tract is genetically selected. Moreover, DNA images by scanning force microscopy, show evidence of a sequence-dependent adhesion of curved DNA tracts to inorganic crystal surfaces. In particular, mica shows a large affinity towards the TT-rich dinucleotide sequences. This suggests a possible mechanism of selection of curved DNA regions, characterized by AA.TT dinucleotides in phase with double-helical periodicity, in the very early evolution steps.

DNA↗

PubMed2003

Systematic search for compact structures of telomeric nucleosomes.

Telomeres are structures functionally and structurally distinct from bulk chromatin. They are constituted of highly conserved 5-7 bp tandemly repeated units, organized into nucleosomes with short linkers, whereas the knowledge of the linker histone role in telomeric chromatin is still fragmentary. Experimental evidence suggests the structural organization of telomeric nucleosomes is different from that of the bulk chromatin. This work presents a systematic search of the telomeric nucleosome arrangements. A low-resolution molecular model was used to evaluate the relative nucleosome packing energy. Structures with favorable energy were found, reducing the possible telomeric chromatin conformations to two different three-dimensional folds.

Anisotropy↗

PubMed2002

Sequence-dependent DNA curvature and flexibility from scanning force microscopy images.

This paper reports a study of the sequence-dependent DNA curvature and flexibility based on scanning force microscopy (SFM) images. We used a palindromic dimer of a 1878-bp pBR322 fragment and collected a large pool of SFM images. The curvature of each imaged chain was measured in modulus and direction. It was found that the ensemble curvature modulus does not allow the separation of static and dynamic contributions to the curvature, whereas the curvature, when its direction in the two dimensions is taken into account, permits the direct separation of the intrinsic curvature contributions static and dynamic contributions. The palindromic symmetry also acted as an internal gauge of the validity of the SFM images statistical analysis. DNA static curvature resulted in good agreement with the predicted sequence-dependent intrinsic curvature. Furthermore, DNA sequence-dependent flexibility was found to correlate with the occurrence of A.T-rich dinucleotide steps along the chain and, in general, with the normalized basepair stacking energy distribution.

Biophysical Phenomena↗

PubMed2002

Sequence-dependent DNA dynamics by scanning force microscopy time-resolved imaging.

Scanning force microscopy was used to study in fluid the conformational fluctuations of two double-stranded DNA molecules resulting from differently cut pBR322 circular DNAs. A new approach was conceived to monitor the thermodynamic equilibrium of the chain dynamics on different scale lengths. This method made it possible to demonstrate that both the observed DNA molecules were allowed to equilibrate only on their local small-scale dynamics during the time of the experiment. This capability of monitoring the length scale and the time scale of the equilibration processes in the dynamics of a DNA chain is relevant to give an insight in the thermodynamics of the DNA binding with proteins and synthetic ligands. It was also shown that the small-scale equilibration of the DNA chain during surface-restricted dynamics is enough to allow a valid measurement of the local sequence-dependent curvature.

Base Sequence↗