Showing papers on "Structural biology published in 1989"

The Structural Biology of CD2

Abstract: The CD2 molecule is a 50-55KD transmembrane glycoprotein expressed on the vast majority of thymocytes and virtually all peripheral T lymphocytes. Its functions are two-fold: adhesion and activation. CD2 serves to facilitate conjugate formation between the T-lineage cell and its cognate partner via intermolecular interaction of CD2 and LFA-3 on the former and latter cells, respectively. Perturbation of the CD2 extracellular segment by certain combinations of anti-CD2 MAbs or LFA-3 and a single anti-CD2 MAb activate T-lineage function. These CD2-mediated activation events also synergize with signals mediated through the TCR to augment T-cell response. Based on microchemical analysis of immunoaffinity-purified human CD2 and cDNA and genomic cloning of mouse and human molecules, considerable structural information is now available. The mature surface human CD2 molecule consists of 327 amino acids: a 185 aa extracellular segment; a 25 aa hydrophobic transmembrane segment; and a 117 aa cytoplasmic domain rich in prolines and basic residues. The CD2 gene is comprised of five exons which span approximately 12 Kb on chromosome 1. A similar protein structure and gene exon organization is found for the mouse CD2 homologue. The CD2 adhesion domain is approximately 103 aa in length and is encoded by a single exon (exon 2). This domain is resistant to proteolysis, even though it lacks any intrachain disulfides and, like the entire extracellular segment protein expressed in a baculovirus system, binds to its cellular ligand, LFA-3. The latter occurs with a micromolar Kd. This relatively low affinity suggests that multivalent interactions among CD2 monomers on the T cells and individual LFA-3 structures on the cognate partner are important in enhancing the avidity of the T-cell interaction with its target or stimulator cell. The affinity of the CD2 extracellular segment for LFA-3 is not affected by truncations in the CD2 cytoplasmic domain, implying that ligand binding is not regulated by intracellular mechanisms. Given that CD2 mRNA expression and surface CD2 copy number are increased by more than one order of magnitude post-TCR stimulation, it is more likely that adhesion via CD2 is modulated by alteration in surface copy number. Analysis of early transduction events occurring via CD3-Ti (TCR) and CD2 including single channel Ca2+ patch-clamp recordings on living human T lymphocytes indicate a virtual identity of signals.(ABSTRACT TRUNCATED AT 400 WORDS)

The Development of the Prediction of Protein Structure

Abstract: The tenet of structural biology that function follows form had its seeds in the monograph by C. B. Anfinsen, The Molecular Basis of Evolution (Anfinsen, 1959), wherein he stated “Protein chemists naturally feel that the most likely approach to the understanding of cellular behavior lies in the study of structure and function of protein molecules.” The achievement of protein crystallography over the past 30 years has confirmed this view whereby the description of the structure and function of proteins is now frequently understood at the atomic level.

Advances in protein design, international workshop 1988

Abstract: Part 1: Methods and theoretical concepts: thermodynamic and kinetic aspects of the folding and self-assembly of proteins folding of peptide fragments in water solution - implications for initiation of protein folding determination of protein structures by NMR - approaches towards extending the limits new developments in protein crystallography a computational tool for structural biology - crystallographic refinement by simulated annealing knowledge-based protein modelling and design computer aided protein design - methods and applications computer simulations applied to site specific mutagenesis and ligand binding - the use of free energy perturbation methods. Part 2 Protein design with (industrial) enzymes: three dimensional structure determination of proteins in PERI engineering of RNase T1 tertiary structure of xylanase and estimation of active sites by site directed mutegenesis modification of milk-clotting aspartic proteases, chymosin and mucor rennin towards the construction of new proteins lacate dehydrogenase - effect of amino acid changes of properties protein engineering of human Lysozyme design and structures of disulfide containing subtilisin variants. Part 3 Protein design with biological response modifiers, including antibodies and protease inhibitors: design of novel insulins with changed self-association and ligand binding properties human glycoproteins and derived variants from recombinant mammalian cell lines the crossover linker - mechanisms and applications in gene modification structure-function relationship in parathyroid hormone structural and functional aspects of protein - protein interaction as studied through crystal structure of subtilisin complexed with its trapped substate SS1 genetic engineering of protease inhibitors, a1-antitrypsin and hirudin design of efficient human leukocyte elastase inhibitors - variants of human pancreatic secretory trysin inhibitor characterization of engineered proteins - some critical reflections.

Understanding the Specificity of the Dihydrofolate Reductase Binding Site

Abstract: Recent developments in molecular and structural biology have transformed our ability to explore the structure-function relationships of biological macromolecules. This applies escpecially to the intermolecular interactions which form the basis of biological specificity. It is now possible to make precisely defined structural changes to each partner in these interactions, by genetic or chemical means, and the spectroscopic and crystallographic methods are available to assess the consequences of these changes in detail. As a result, it is now beginning to become possible to make quantitative estimates of the contributions of individual interactions to the overall molecular recognition process.