946,828 research outputs found

    Minireview: Protein Interactions

    Get PDF

    Length, Protein-Protein Interactions, and Complexity

    Full text link
    The evolutionary reason for the increase in gene length from archaea to prokaryotes to eukaryotes observed in large scale genome sequencing efforts has been unclear. We propose here that the increasing complexity of protein-protein interactions has driven the selection of longer proteins, as longer proteins are more able to distinguish among a larger number of distinct interactions due to their greater average surface area. Annotated protein sequences available from the SWISS-PROT database were analyzed for thirteen eukaryotes, eight bacteria, and two archaea species. The number of subcellular locations to which each protein is associated is used as a measure of the number of interactions to which a protein participates. Two databases of yeast protein-protein interactions were used as another measure of the number of interactions to which each \emph{S. cerevisiae} protein participates. Protein length is shown to correlate with both number of subcellular locations to which a protein is associated and number of interactions as measured by yeast two-hybrid experiments. Protein length is also shown to correlate with the probability that the protein is encoded by an essential gene. Interestingly, average protein length and number of subcellular locations are not significantly different between all human proteins and protein targets of known, marketed drugs. Increased protein length appears to be a significant mechanism by which the increasing complexity of protein-protein interaction networks is accommodated within the natural evolution of species. Consideration of protein length may be a valuable tool in drug design, one that predicts different strategies for inhibiting interactions in aberrant and normal pathways.Comment: 13 pages, 5 figures, 2 tables, to appear in Physica

    ProDGe: investigating protein-protein interactions at the domain level

    Get PDF
    An important goal of systems biology is the identification and investigation of known and predicted protein-protein interactions to obtain more information about new cellular pathways and processes. Proteins interact via domains, thus it is important to know which domains a protein contains and which domains interact with each other. Here we present the Java^TM^ program ProDGe (Protein Domain Gene), which visualizes existing and suggests novel domain-domain interactions and protein-protein interactions at the domain level. The comprehensive dataset behind ProDGe consists of protein, domain and interaction information for both layers, collected and combined appropriately from UniProt, Pfam, DOMINE and IntAct. Based on known domain interactions, ProDGe suggests novel protein interactions and assigns them to four confidence classes, depending on the reliability of the underlying domain interaction. Furthermore, ProDGe is able to identify potential homologous interaction partners in other species, which is particularly helpful when investigating poorly annotated species. We further evaluated and compared experimentally identified protein interactions from IntAct with domain interactions from DOMINE for six species and noticed that 31.13% of all IntAct protein interactions in all six species can be mapped to the actual interacting domains. ProDGe and a comprehensive documentation are freely available at http://www.cogsys.cs.uni-tuebingen.de/software/ProDGe

    Hydrodynamic Interactions in Protein Folding

    Full text link
    We incorporate hydrodynamic interactions (HI) in a coarse-grained and structure-based model of proteins by employing the Rotne-Prager hydrodynamic tensor. We study several small proteins and demonstrate that HI facilitate folding. We also study HIV-1 protease and show that HI make the flap closing dynamics faster. The HI are found to affect time correlation functions in the vicinity of the native state even though they have no impact on same time characteristics of the structure fluctuations around the native state

    Energetics of Protein-DNA Interactions

    Get PDF
    Protein-DNA interactions are vital for many processes in living cells, especially transcriptional regulation and DNA modification. To further our understanding of these important processes on the microscopic level, it is necessary that theoretical models describe the macromolecular interaction energetics accurately. While several methods have been proposed, there has not been a careful comparison of how well the different methods are able to predict biologically important quantities such as the correct DNA binding sequence, total binding free energy, and free energy changes caused by DNA mutation. In addition to carrying out the comparison, we present two important theoretical models developed initially in protein folding that have not yet been tried on protein-DNA interactions. In the process, we find that the results of these knowledge-based potentials show a strong dependence on the interaction distance and the derivation method. Finally, we present a knowledge-based potential that gives comparable or superior results to the best of the other methods, including the molecular mechanics force field AMBER99

    Protein-carbohydrate interactions during fertilization

    Get PDF
    Interaction between gametes during fertilization is at least in part regulated by carbohydrate moieties of the zona pellucida (ZP) and carbohydrate binding proteins of the sperm surface. This review focuses on the protein-carbohydrate interactions during the primary binding of the sperm to the ZP in different species. Synthesis, structure and composition of the ZP an summarized. The functional significance of carbohydrate residues of the ZP as sperm receptor is discussed. Sperm surface proteins known to have specific ZP and carbohydrate-binding sites including the mouse beta 1,4-galactosyltransferase and sp56, the rabbit protein Sp17, a human mannose-binding protein and several members of the sperm-adhesin family are presented

    Exploitation of proteomics strategies in protein structure-function studies

    Get PDF
    Mass spectrometry plays a central role in structural proteomics, particularly in highly intensive structural genomics projects. This review paper reports some examples taken from recent work from the authors' laboratory and is aimed at showing that modem proteomics strategies are instrumental in the integration of structural genomic projects in fields such as: (i) protein-protein interactions, (ii) protein-DNA interactions, (iii) protein-ligand interactions, and (iv) protein-folding intermediates
    corecore