A5015057310- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Retinal Development and Disorders
- Enzyme Structure and Function
- interferon and immune responses
- Erythrocyte Function and Pathophysiology
- Protein Structure and Dynamics
- Amino Acid Enzymes and Metabolism
- Peptidase Inhibition and Analysis
- Poxvirus research and outbreaks
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
- Plant Reproductive Biology
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Mass Spectrometry Techniques and Applications
- Calcium signaling and nucleotide metabolism
- Herpesvirus Infections and Treatments
- Crystallization and Solubility Studies
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- Connexins and lens biology
- Biochemical and Structural Characterization
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
Trinity College Dublin
2013-2024
Boston Children's Hospital
2020-2023
Yale University
2002-2022
Trinity College
2019
University College Dublin
2017
22q11 Ireland
2017
University of California, Santa Barbara
2015-2016
McGill University
2015-2016
University of California, Irvine
2015-2016
American University
2015-2016
Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe lineage expressing broadly neutralizing influenza virus antibodies derived from subject immunized with the 2007 trivalent vaccine. The comprises three mature antibodies, unmutated common ancestor, and intermediate. Their heavy-chain complementarity determining region inserts into conserved receptor-binding pocket of HA. show analysis structures,...
Myosin Va is a widely expressed actin-based motor protein that binds members of the Rab GTPase family (3A, 8A, 10, 11A, 27A) and implicated in many intracellular trafficking processes. To our knowledge, myosin has not been tested systematic screen for interactions with entire family. end, we report yeast two-hybrid all human Rabs Va-binding ability reveal 10 novel (3B, 3C, 3D, 6A, 6A', 6B, 11B, 14, 25, 39B), which include three new subfamilies (Rab6, Rab14, Rab39B). Of interest, interacts...
Rab8a is associated with the dynamic regulation of membrane protrusions in polarized cells. one several Rab GTPases that are substrates leucine-rich repeat kinase 2 (LRRK2), a serine/threonine linked to Parkinson's disease. phosphorylated at T72 (pT72) its switch helix and recruits phospho-specific effector RILPL2, which subsequently regulates ciliogenesis. Here, we report crystal structure phospho-Rab8a (pRab8a) complex RH2 (RILP homology) domain RILPL2. The heterotetramer RILPL2 forming...
Abstract A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed accurately predict combinations of mutations that maintain or enhance function. Models co-variation (e.g., EVcouplings), which leverage extensive information about various activities from homologous sequences, have proven effective for many applications...
Abstract The crystal structure of the human class I MHC molecule HLA-A2 complexed with an octameric peptide, Tax8 (LFGYPVYV), from T cell lymphotrophic virus-1 (HTLV-1) has been determined. This is compared a newly refined, higher resolution (1.8 Å) nonameric Tax9 peptide (LLFGYPVYV) one more N-terminal residue. Despite absence residue (P1) bound in conserved peptide-binding pocket Tax8/HLA-A2 complex, structures two complexes are essentially identical. Water molecules complex replace...
The design of inhibitors with enhanced potency against proteolytic enzymes has many applications for the treatment human diseases. In addition to optimization chemical interactions between enzyme and inhibitor, binding affinity can be increased by constraining inhibitor conformation that is recognized enzyme, thus lowering entropic barrier complex formation. We have structurally characterized complexes a macrocyclic pentapeptide its acyclic analogue penicillopepsin, an aspartic proteinase,...
Here, we provide the first structural characterization of host-guest complexation between cucurbit[7]uril (Q7) and dimethyllysine (KMe2 ) in a model protein. Binding was dominated by complete encapsulation dimethylammonium functional group. While selectivity for most sterically accessible observed both solution solid state, three different modes Q7-KMe2 were revealed X-ray crystallography. The crystal structures also entrapped water molecules that solvated ammonium group within Q7 cavity....
LRRK2 is a multi-domain Ser/Thr kinase that associated with inherited and sporadic cases of Parkinson's disease. Many mutations linked to disease are within central ROC-COR regulatory region the subsequent domain, leading enhanced catalytic activity. The N-terminus human consists armadillo repeat motifs (ARMs) followed by ankyrin repeats (ANKs). Recently, Rab GTPases have emerged as key players in function, both substrates kinase, regulators Rabs recruit effector proteins via their...
Val-->Ala mutations within the effective transmembrane segment of a model single-spanning membrane protein, 50-residue major coat (gene VIII) protein bacteriophage M13, are shown to have sequence-dependent impacts on stabilization membrane-embedded helical dimeric structures. Randomized mutagenesis performed hydrophobic 21-39 (YIGYAWAMV-VVIVGATIGI) produced library viable mutants which included those in each four valine residues was replaced by an alanine residue. Significant variations...
Rab11‐FIP3 is an endosomal recycling compartment (ERC) protein that implicated in the process of membrane delivery from ERC to sites insertion during cell division. Here we report critical for structural integrity interphase. We demonstrate knockdown and expression a mutant Rab11‐binding deficient cause loss all ERC‐marker staining pericentrosomal region A431 cells. Furthermore, find fluorophore‐labelled transferrin cannot access cells which function has been perturbed. this appears be...
Dissimilatory sulfite reductases (dSiRs) are crucial enzymes in bacterial sulfur-based energy metabolism, which is likely to have been present some of the earliest life forms on Earth. Several classes dSiRs proposed basis different biochemical and spectroscopic properties. Here, we describe first structure a dSiR from desulforubidin (Drub) class isolated Desulfomicrobium (Dm.) norvegicum. The assembled as a2b2c2, two DsrC proteins bound core [DsrA]2[DsrB]2 unit, reported for desulfoviridin...
The Rab family of small GTPases regulate various aspects cellular dynamics in eukaryotic cells. Membrane trafficking has emerged as central to the functions leucine-rich repeat kinase 2 (LRRK2), which is associated with inherited and sporadic forms Parkinson's disease (PD). Rabs act both regulators catalytic activity targets for serine/threonine phosphorylation by LRRK2. Rab32, Rab38 Rab29 have been shown LRRK2 sub-cellular localization through direct interactions. Recently, was escort Golgi...
Abstract Rab GTPases are master regulators of membrane trafficking in eukaryotic cells. Phosphorylation was characterized the 1990s and there have been intermittent reports its relevance to functions. as a regulatory mechanism has gained prominence through identification Rabs physiological substrates leucine‐rich repeat kinase 2 (LRRK2). LRRK2 is Ser/Thr that associated with inherited sporadic forms Parkinson disease. In recent years, numerous kinases their signaling pathways identified lead...
We have sequenced the <i>Streptomyces plicatus</i> β-<i>N</i>-acetylhexosaminidase (<i>Sp</i>Hex) gene and identified encoded protein as a member of family 20 glycosyl hydrolases. This includes human β-<i>N</i>-acetylhexosaminidases whose deficiency results in various forms G<sub>M2</sub> gangliosidosis. Based upon x-ray structure <i>Serratia marcescens</i> chitobiase (<i>Sm</i>Chb), we generated three-dimensional model of<i>Sp</i>Hex by comparative molecular modeling. The overall enzyme is...