A5044066352- interferon and immune responses
- DNA and Nucleic Acid Chemistry
- Cell Adhesion Molecules Research
- Mitochondrial Function and Pathology
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- ATP Synthase and ATPases Research
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Chemical Synthesis and Analysis
- Systemic Lupus Erythematosus Research
- Genetic Neurodegenerative Diseases
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Chemokine receptors and signaling
- thermodynamics and calorimetric analyses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Heparin-Induced Thrombocytopenia and Thrombosis
- S100 Proteins and Annexins
- Bacteriophages and microbial interactions
- Complement system in diseases
Trellis Bioscience (United States)
2023
Helix Biomedix (United States)
2023
Helix Biostructures (United States)
2023
Albert Einstein College of Medicine
2015-2022
The University of Texas Health Science Center at San Antonio
2012-2015
Utrecht University
2004-2009
Rockefeller University
2007
University of Ioannina
2001-2006
Rutgers, The State University of New Jersey
2006
University of Wisconsin–Madison
2004
Interaction of regulatory DNA binding proteins with their target sites is usually preceded by to nonspecific DNA. This speeds up the search for site several orders magnitude. We report solution structure and dynamics complex a dimeric lac repressor domain The same set residues can switch roles from purely electrostatic interaction backbone in highly specific mode base pairs cognate operator sequence. protein-DNA interface flexible on biologically relevant time scales that may assist rapid...
An innovative approach for a rare disease Charcot-Marie-Tooth type 2A (CMT2A) is rare, inherited neurodegenerative condition. Affected individuals develop severe progressive muscle weakness, motor deficits, and peripheral neuropathy. Although defects in the gene encoding mitofusin 2 (MFN2) are known to cause CMT2A, remains incurable. Rocha et al. identified specific MFN2 residues contributing developed class of MFN2-agonist drugs. The small molecules restored mitochondrial fusion activity...
Neutrophils constitute the first line of cellular defense in response to bacterial and fungal infections rely on granular proteins kill microorganisms, but uncontrolled secretion neutrophil cargos is injurious host should be closely regulated. Thus, increased plasma levels secretory proteins, including myeloperoxidase elastase, are associated with tissue damage hallmarks systemic inflammation. Here, we describe a novel high-throughput screening approach identify small molecule inhibitors...
Abstract Mitofusins reside on the outer mitochondrial membrane and regulate fusion, a physiological process that impacts diverse cellular processes. are activated by conformational changes subsequently oligomerize to enable fusion. Here, we identify small molecules directly increase or inhibit mitofusins activity modulating mitofusin conformations oligomerization. We use these better understand role of in function, signaling. find activation increases, whereas inhibition decreases fusion...
Tripartite motif protein TRIM5α blocks retroviral replication after cell entry, and species-specific differences in its activity are determined by sequence variations within the C-terminal B30.2/PRYSPRY domain. Here we report a high-resolution structure of PRYSPRY domain, rhesus monkey that potently restricts HIV infection, identify features involved interaction with capsid. The extensive capsid-binding interface maps on structurally divergent face formed hypervariable loop segments,...
Members of the tripartite motif (TRIM) protein family RING E3 ubiquitin (Ub) ligases promote innate immune responses by catalyzing synthesis polyubiquitin chains linked through lysine 63 (K63). Here, we investigate mechanism which TRIM5α retroviral restriction factor activates Ubc13, K63-linkage-specific E2. Structural, biochemical, and functional characterization TRIM5α:Ubc13-Ub interactions reveals that activation Ubc13-Ub conjugate requires dimerization domain. Our data explain how...
Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by deficiency in functional C1 esterase inhibitor, serpin family protein that blocks the activity of plasma kallikrein. Insufficient inhibition kallikrein results overproduction bradykinin, vasoactive inflammatory mediator produces both pain and unpredictable swelling during HAE attacks, with potentially life-threatening consequences. We describe generation STAR-0215, humanized IgG1 antibody long circulating half-life...
The BCL-2 protein family plays a critical role in regulating cellular commitment to mitochondrial apoptosis. Pro-apoptotic Bcl-2-associated X (BAX) is an executioner of the that represents gateway Following stresses induce apoptosis, cytosolic BAX activated and translocates mitochondria, where it inserts into outer membrane form toxic pore. How activation pathway proceeds how this may be inhibited not yet completely understood. Here we describe synthetic antibody fragments (Fabs) as...
The platelet integrin receptor α IIb β 3 plays a critical role in thrombosis and haemostasis by mediating interactions between platelets several ligands but primarily fibrinogen. It has been shown previously that the YMESRADR KLAEVGRVYLFL (313–332) sequence of subunit an important activation, fibrinogen binding ‐mediated outside‐in signalling. Furthermore, we recently showed 20‐residue peptide (20‐mer) 313–332, is potent inhibitor aggregation to , interacting with rather than receptor. In...
Abstract The ability of an integrin to distinguish between the RGD‐containing extracellular matrix proteins is thought be due partially variety RGD conformations. Three criteria have been proposed for evaluation structure–activity relationship peptides. These include: (i) distance charged centres, (ii) Arg C β and Asp atoms, (iii) pseudo‐dihedral angle defining side‐chain orientation formed by ζ , α γ atoms. A comparative conformation–activity study was performed linear peptides strongly...
α IIb β 3 , a member of the integrin family adhesive protein receptors, is most abundant glycoprotein on platelet plasma‐membranes and binds to proteins via recognition short amino acid sequences, for example ubiquitous RGD motif. However, elucidation ligand‐binding domains receptor remains controversial, mainly owing fact that integrins are conformationally labile during purification storage. In this study, detailed mapping extracellular region subunit presented, using overlapping...
Abstract According to general belief, the conformational information on short linear peptides in solution derived at ambient temperature from NMR spectrometry represents a population‐weighted average over all members of an ensemble rapidly interconverting conformations. Usually search for discrete conformations is concentrated low temperatures especially when sharp resonances are detected room temperature. Using peptide Ac–RGD–NH 2 (Ac–Arg–Gly–Asp–NH , Ac: acetyl) as model system and...
Summary Mitochondrial fusion is a physiological process that regulated by mitofusins on the outer mitochondrial membrane. Conformational plasticity between anti- and pro-tethering conformations of permits tethering subsequent fusion. Here we developed pharmacophore-based model to rationally manipulate conformational mitofusin 2 perfomed an in silico small-molecule screen. This enabled discovery direct activator mitofusins, MASM7, capable potently promoting The specificity MASM7-mitofusin...
Abstract Synthetic carriers play an important role in immunogen presentation, due to their ability of inducing improved and specific responses conjugated epitopes. Their influence on the bioactive conformation epitope, though admittedly crucial for relevant vitro vivo applications, is difficult evaluate, given usual lack information complex conformational features determined by nature carrier mode ligation. Using Herpes simplex virus glycoprotein D‐1 epitope (Leu 9...
Members of the tripartite motif (TRIM) protein family RING E3 ubiquitin (Ub) ligases promote innate immunity responses by catalyzing synthesis K63-linked polyubiquitin chains in a manner that is dependent on either direct or indirect interaction with pathogen-associated molecular patterns. In this study we investigate mechanism, which TRIM5α retroviral restriction factor activates Ubc13, K63-linkage specific E2 Ub-conjugating enzyme. Structural, biochemical and functional characterization...