Ann M Dixon

• PhD
• Professor at University of Warwick

Cyclic peptides are increasingly important structures in drugs but their development can be impeded by difficulties associated with their synthesis. Here, we introduce the 3‐aminoazetidine (3‐AAz) subunit as a new turn‐inducing element for the efficient synthesis of small head‐to‐tail cyclic peptides. Greatly improved cyclizations of tetra‐, penta‐...

The B-cell receptor (BCR), a complex comprised of a membrane-associated immunoglobulin (mIg) and the Igα/β heterodimer, is one of the most important immune receptors in humans and controls B-cell development, activity, selection, and death. BCR signaling plays key roles in autoimmune diseases and lymphoproliferative disorders yet, despite the clini...

Antibiotic resistance is a significant threat to human health, with natural products remaining the best source for new antimicrobial compounds. Antimicrobial peptides (AMPs) are natural products with great potential for clinical use as they are small, amenable to customization, and show broad‐spectrum activities. Lynronne‐1 is a promising AMP ident...

The reticulon family of integral membrane proteins are conserved across all eukaryotes and typically localize to the endoplasmic reticulum (ER), where they are involved in generating highly-curved tubules. We recently demonstrated that Reticulon-like protein B13 (RTNLB13) from Arabidopsis thaliana contains a curvature-responsive amphipathic helix (...

Peptide-based drugs combine advantages of larger biological therapeutics with those of small molecule drugs, but they generally display poor permeability and metabolic stability. Recently, we introduced a new type of peptide bond isostere, in which the backbone carbonyl is replaced with a 3-amino oxetane heterocycle, into short linear peptides with...

Reticulons are a large family of integral membrane proteins that are ubiquitous in eukaryotes and play a key role in functional remodelling of the endoplasmic reticulum membrane. The reticulon family is especially large in plants, with the Arabidopsis thaliana genome containing twenty-one isoforms. Reticulons vary in length but all contain a conser...

Significance This study demonstrates, in vivo, that reticulon (RTN) proteins, responsible for the shaping and maintenance of endoplasmic reticulum (ER) membrane tubules, rely on a highly conserved C-terminal amphipathic helix (APH) for their morphogenic function. Previously it was thought that RTN could bend the ER membrane both by assuming a wedge...

Due to its applications in the treatment of cancer and autoimmune diseases, the 42 kDa zinc-dependent metalloenzyme carboxypeptidase G2 (CPG2) is of great therapeutic interest. An X-ray crystal structure of unliganded CPG2 reported in 1997 revealed the domain architecture and informed early rational drug design efforts, however further efforts at c...

List of yeast strains used in this study.DOI: http://dx.doi.org/10.7554/eLife.07485.017

Membrane proteins regulate a large number of cellular functions, and have great potential as tools for manipulation of biological systems. Developing these tools requires a robust and quantitative understanding of membrane protein folding and interactions within the bilayer. With this in mind, we have designed a series of proteins to probe the net...

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosacch...

Dendritic cell‐specific intercellular adhesion molecule 3‐grabbing non‐integrin‐related (DC‐SIGNR), also known as liver/lymph node‐specific intercellular adhesion molecule 3‐grabbing non‐integrin, CLEC4M, CD209L, and CD299, is a Ca2+‐dependent lectin that has been implicated in increasing the infection rates of several viruses, including HIV, but t...

DC-SIGNR (dendritic cell-specific ICAM-3-grabbing non-integrin-related, also known as L-SIGN, CLEC4M, CD209L, CD299) is a calcium-dependent lectin that has been implicated in increasing the infection rates of several viruses including HIV, yet the physiological role of DC-SIGNR in healthy cells is currently not known with certainty. A close homolog...

Major histocompatibility complex (MHC) class II molecules exhibit conformational heterogeneity, which influences their ability to stimulate CD4 T cells and drive immune responses. Previous studies suggest a role for the transmembrane domain of the class II αβ heterodimer in determining molecular structure and function. Our previous studies identifi...

The C-type lectin DC-SIGNR (dendritic cell-specific ICAM-3-grabbing non-integrin-related; also known as L-SIGN or CD299) is a promising drug target due to its ability to promote infection and/or within-host survival of several dangerous pathogens (e.g. HIV and severe acute respiratory syndrome coronavirus (SARS)) via interactions with their surface...

Receptor tyrosine kinases bind ligands such as cytokines, hormones, and growth factors and regulate key cellular processes, including cell division. They are also implicated in the development of many types of cancer. One such example is the Neu receptor tyrosine kinase found in rats (homologous to the human ErbB2 protein), which can undergo a vali...

The purpose of this study was to investigate the sequence-dependence of oligomerization of transmembrane domain 2 (TM2) of rat carnitine palmitoyltransferase 1A (rCPT1A), to elucidate the role of this domain in the function of the full-length enzyme. Oligomerization of TM2 was studied qualitatively using complementary genetic assays that facilitate...

The homodimeric E5 protein from bovine papillomavirus activates the platelet-derived growth factor β receptor through transmembrane (TM) helix-helix interactions leading to uncontrolled cell growth. Detailed structural information for the E5 dimer is essential if we are to uncover its unique mechanism of action. In vivo mutagenesis has been used to...

In recent years there has been an abundance of research into the potential of helical peptides to influence cell function. These peptides have been used to achieve a variety of different outcomes from cell repair to cell death, depending upon the peptide sequence and the nature of its interactions with cell membranes and membrane proteins. In this...

The Major Histocompatibility Complex Class II (Class II MHC) and invariant chain (Ii) proteins are key initiators of an immune response to invading pathogens. Following biosynthesis, three MHCalpha/beta hetero-dimers associate with an Ii homotrimer to form a nine-chain protein complex. Only as part of this complex are the MHC molecules exported to...

The platelet-derived growth factor beta-receptor (PDGFbetaR) represents an important subclass of receptor tyrosine kinase (RTK) thought to be activated by ligand-induced dimerization. Interestingly, the receptor is also activated by the bovine papillomavirus E5 oncoprotein, an interaction involving the transmembrane domains of both proteins and res...

Membrane-spanning epidermal growth factor receptor ErbB2 is of key importance in cell division, in which a dimeric complex of the protein is responsible for tyrosine kinase activation following ligand binding. The rat homologue of this receptor (Neu) is prone to a valine to glutamic acid mutation in the transmembrane domain (TM), resulting in perma...

The twin-arginine translocase (Tat) pathway transports folded proteins across bacterial and thylakoid membranes. In Escherichia coli, a membrane-bound TatA complex, which oligomerizes to form complexes of less than 100 to more than 500 kDa, is considered essential for translocation. We have studied the contributions of various TatA domains to the a...

Carnitine palmitoyltransferase 1 (CPT1) controls the rate of entry of long-chain fatty acids into the mitochondrial matrix for beta-oxidation and has been reported to exist as an oligomer. We have investigated the in vivo oligomerization of full-length rat CPT1A (rCPT1A) along with those of the N-terminal truncation/deletion mutants Delta(1-82), De...

The bovine papillomavirus E5 protein (BPV E5) is a 44-amino-acid homodimeric transmembrane protein that binds directly to the transmembrane domain of the platelet-derived growth factor (PDGF) β receptor and induces ligand-independent receptor activation. Three specific features of BPV E5 are considered important for its ability to activate the PDGF...

The E5 protein from bovine papillomavirus is a type II membrane protein and the product of the smallest known oncogene. E5 causes cell transformation by binding and activating the platelet-derived growth factor beta receptor (PDGFbetaR). In order to productively interact with the receptor, it is thought that E5 binds as a dimer. However, wild-type...

The biological importance of membrane proteins has been recognized worldwide for many years, but historically these proteins have proved difficult to characterize structurally because of a variety of experimental challenges. Recently, technological advances across several disciplines have prompted considerable progress in three-dimensional structur...

The transmembrane (TM) domain of the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) has long been implicated in both correct folding and function of the MHC class II complex. To function correctly, Ii must form a trimer, and the TM domain is one of the domains thought to stabilize the trimeric state. Specific mutati...

The 44 amino acid E5 transmembrane protein is the primary oncogene product of bovine papillomavirus. Homodimers of the E5 protein activate the cellular PDGF beta receptor tyrosine kinase by binding to its transmembrane domain and inducing receptor dimerization, resulting in cellular transformation. To investigate the role of transmembrane hydrophil...

Growth factor receptors are typically activated by the binding of soluble ligands to the extracellular domain of the receptor, but certain viral transmembrane proteins can induce growth factor receptor activation by binding to the receptor transmembrane domain. For example, homodimers of the transmembrane 44-amino acid bovine papillomavirus E5 prot...

this article can be found at doi: 10.1016/j.jmb.2004.03.044 E-mail address of the corresponding author: daniel.dimaio@yale.edu Abbreviations used: PDGF, platelet-derived growth factor; CAT, chloramphenicol acetyltransferase

The folding of alpha-helical membrane proteins has previously been described using the two stage model, in which the membrane insertion of independently stable alpha-helices is followed by their mutual interactions within the membrane to give higher order folding and oligomerization. Given recent advances in our understanding of membrane protein st...

The preferred conformations and conformational flexibilities of the trisaccharides alpha-D-Glcp-(1-->2)-beta-D-Glcp-(1-->3)-alpha-D-Glcp-OMe (I) and alpha-D-Glcp-(1-->3)[beta-D-Glcp-(1-->4)]-alpha-D-Glcp-OMe (II) in aqueous solution were determined using nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) and Langevin dynamics (L...

A peptide fragment from a protein hairpin turn region was modified by addition of isoleucine residues to both ends to enhance binding to lipid micelles; the resulting peptide (I(1)-I(2)-C(3)-N(4)-N(5)-P(6)-H(7)-I(8)-I(9)) contains the core sequence I-C-N-N-P-H from an antibody-binding region of hemagglutinin A. Nuclear magnetic resonance (NMR) diff...

The determination of the absolute configuration of deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus toward the synthesis of P-stereodifined phosphorothioated oligodeoxyribonucleotides is easily accomplished with computer-assisted molecular modeling and M-GOESY NMR spectroscopy. Specifically, computer-modeling diasteromeric phosphoram...

One-dimensional nuclear magnetic resonance techniques were applied to the conformational investigation of a disaccharide. More specifically, nuclear Overhauser enhancements (NOEs) of protons on either side of the glycosidic bond have been used to determine the conformation of the disaccharide alpha-l-Rhap-(1 --> 2)-alpha-l-Rhap-OMe. A modified GOES...

Gram quantities of aquatic humic substances (AHS) were extracted from the Wakarusa River−Clinton Lake Reservoir system, near Lawrence, KS, to support nuclear magnetic resonance (NMR) experimental studies, report concentrations of dissolved organic carbon (DOC) and AHS, define sources of the AHS, and determine if the AHS yield sufficient quantities...

Gram quantities of aquatic humic substances (AHS) were extracted from the Wakarusa River−Clinton Lake Reservoir system, near Lawrence, KS, to support nuclear magnetic resonance (NMR) experimental studies, report concentrations of dissolved organic carbon (DOC) and AHS, define sources of the AHS, and determine if the AHS yield sufficient quantities...

The use of the computer program CONTIN to analyze pulsed-field gradient NMR (PFG-NMR) data for several standard humic and fulvic acids is described. An advantage of PFG-NMR analysis is that integration of different spectral regions provides a picture of how the diffusion coefficients vary with functional group composition for a given sample. Using...

The nuclear magnetic resonance (NMR) methods for spectral simplication, which can be used in the analysis of complex mixtures, are summarized. These methods can be employed to gain information about the structural components of a mixture, to resolve the components of a mixture, and to characterize binding interactions that take place in solutions o...

The association of 4‘-fluoro-1‘-acetonaphthone (F-acetonaphthone) with the International Humic Substances Society (I.H.S.S.) Suwannee River fulvic acid (SRFA) standard in 55% CH3OD/45% D2O was investigated as a function of SRFA concentration (4.5−13.5 mg/mL) as well as solution pαH* (3.88−7.56). 19F NMR measurements of T1 and T2 relaxation times we...

The relaxation rate ratio method (RRR) has been used to calculate molecular correlation times, tau(c), from the C-13 and Cd-113 relaxation rates of cadmium-cyclohexanediamine tetraacetate (CyDTA). The ratio of spin-spin (R-2) relaxation rates to spin-lattice (R-1) relaxation rates (R-2/R-1) is used to determine the relative motion of specific nucle...

To simplify the complex 1H NMR spectrum of a fulvic acid sample and gain structural and molecular size information, spectral editing techniques were used in conjunction with a general PFG NMR pulse sequence. These editing techniques exploit differences in T1 and T2 relaxation times as well as differences in coupling constants. The experiments were...