A5039120138- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- SARS-CoV-2 and COVID-19 Research
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Chemokine receptors and signaling
- Photosynthetic Processes and Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Phylogenetic Studies
- ATP Synthase and ATPases Research
- Erythrocyte Function and Pathophysiology
- Chemical Synthesis and Analysis
- Hemoglobin structure and function
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- COVID-19 Clinical Research Studies
- Neuropeptides and Animal Physiology
- Escherichia coli research studies
Vanderbilt University
2016-2021
University of Wisconsin–Madison
2012-2017
University of Minnesota
2004
University of Virginia
2004
The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2), a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack thorough understanding mechanisms humoral immunity SARS-CoV-24. Here analyse large panel human monoclonal antibodies that target spike (S) glycoprotein5, identify several exhibit potent neutralizing activity fully block receptor-binding...
Significance The transmembrane helices of single-span membrane proteins are commonly engaged in oligomeric interactions that essential for structure and function. These often occur the form recurrent structural motifs. Here we present an analysis one most important motifs (GAS right ), showing its geometry is optimized to carbon hydrogen bonds at helix−helix interface. reveals basis characteristic GxxxG sequence signature. We built upon analysis, creating a method predicts known GAS...
We used fluorescence resonance energy transfer (FRET) to detect and quantitate the interaction of sarcoplasmic reticulum Ca-ATPase (SERCA) with phospholamban (PLB) in membranes. PLB inhibits SERCA only at submicromolar Ca. It has been proposed that relief inhibition micromolar Ca is due dissociation inhibitory complex. To test this hypothesis, we co-reconstituted donor-labeled acceptor-labeled I40A-PLB (superinhibitory, monomeric mutant) membranes defined lipid protein composition, full...
A range of membrane protein modeling tools has been developed in the past 5-10 years, yet few these are integrated and make use existing functionality for soluble proteins. To extend methods Rosetta biomolecular suite proteins, we recently implemented RosettaMP, a general framework modeling. While RosettaMP facilitates implementation new methods, addressing real-world biological problems also requires set accessory that used to carry out standard tasks.Here, present six tools, including de...
The GxxxG motif is frequently found at the dimerization interface of a transmembrane structural called GASright, which characterized by short interhelical distance and right-handed crossing angle between helices. In GASright dimers, such as glycophorin A (GpA), BNIP3, members ErbB family, backbones helices are in contact, they invariably display networks 4 to 8 weak hydrogen bonds Cα–H carbon donors carbonyl acceptors on opposing (Cα–H···O═C bonds). These helix–helix presumably stabilizing,...
Abstract We present the Molecular Software Library (MSL), a C++ library for molecular modeling. MSL is set of tools that supports large variety algorithms design, modeling, and analysis macromolecules. Among main features supported by are methods applying geometric transformations alignments, implementation rich energy functions, side chain optimization, backbone manipulation, calculation solvent accessible surface area, other tools. has number unique features, such as ability storing...
Interactions between α-helices within the hydrophobic environment of lipid bilayers are integral to folding and function transmembrane proteins; however, major forces that mediate these interactions remain debated, our ability predict is still largely untested. We recently demonstrated frequent association motif GASright, GxxxG-containing fold glycophorin A dimer, optimal for formation extended networks Cα–H hydrogen bonds, supporting hypothesis bonds contributors association. also found...
We have used time-resolved phosphorescence anisotropy (TPA) to probe rotational dynamics of the rabbit skeletal sarcoplasmic reticulum Ca-ATPase (SERCA), test hypothesis, generated from X-ray crystallography, that large-scale structural changes are induced by Ca in this system. Previous TPA studies on SERCA primarily erythrosin 5'-isothiocyanate (ErITC), which binds nucleotide-binding domain and inactivates enzyme. To investigate active enzyme, we labeled with 5'-iodoacetamide,...
Partial covalent interactions (PCIs) in proteins, which include hydrogen bonds, salt bridges, cation-π, and π-π interactions, contribute to thermodynamic stability facilitate with other biomolecules. Several score functions have been developed within the Rosetta protein modeling framework that identify evaluate these PCIs through analyzing geometry between participating atoms. However, we hypothesize can be unified a simplified electron orbital representation. To test this hypothesis,...
Abstract The mechanisms and regulation of neurotransmitter release is a complex process involving many co-factors proteins. One critical interaction the exocytosis when G-protein βγ (Gβγ) dimers bind to soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. comprised protein-25 (SNAP-25), syntaxin 1A, synaptobrevin. Herein we probe across entire family human Gβ Gγ proteins for residues with SNARE, by systematically screening peptide sequences their ability...
Neuronal G-protein βγ heterodimers (Gβγ) inhibit the final step of synaptic vesicle fusion upon binding to N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. The ternary SNARE complex is composed synaptosomal-associated protein, 25kDa (SNAP-25), syntaxin 1A, and synaptobrevin. general mechanism underlying Gβγ-mediated inhibition involves Ca2+-dependent competition with Ca2+-sensor synaptotagmin (syt) for binding. However, molecular determinants formation thus...