A5070291410- Lipid Membrane Structure and Behavior
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Immune Response and Inflammation
- Antimicrobial Peptides and Activities
- Protein Structure and Dynamics
- Supramolecular Self-Assembly in Materials
- RNA and protein synthesis mechanisms
- Sarcoma Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Hedgehog Signaling Pathway Studies
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Lymphatic System and Diseases
- Soft tissue tumor case studies
- Cancer Cells and Metastasis
- Soft tissue tumors and treatment
- Cardiac electrophysiology and arrhythmias
- Cancer-related gene regulation
- Viral Infectious Diseases and Gene Expression in Insects
- Ion channel regulation and function
- Advanced biosensing and bioanalysis techniques
University of California, San Francisco
2015-2024
Scripps Research Institute
2021-2024
Orthopaedic Hospital
2014-2015
University of California, Los Angeles
2014-2015
University of California System
2014
Precise packing for membrane proteins Although nonpolar amino acid side chains pack efficiently in proteins, it has been difficult to determine how much this contributes protein stability. Designed have largely relied on other stabilizing interactions such as metal-ligand and hydrogen bonds. Mravic et al. uncovered a steric code underlying the folding of natural phospholamban, which they used design stable with interfaces. They suggest that residues plays role stability many proteins....
Ubiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast humans. However, recent deep sequencing studies indicate that ubiquitin highly tolerant to single mutations. We hypothesized this tolerance would be reduced by chemically induced physiologic perturbations. To test hypothesis, a class of first year UCSF graduate students employed mutational scanning determine the fitness landscape all possible residue mutations presence five different small...
The folding of natural proteins typically relies on hydrophobic packing, metal binding, or disulfide bond formation in the protein core. Alternatively, a 3D structure can be defined by incorporating multivalent cross-linking agent, and this approach has been successfully developed for selection bicyclic peptides from large random-sequence libraries. By contrast, there is no general method de novo computational design multicross-linked with predictable well-defined folds, including ones not...
Introduction. Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear line differentiation, although most presumed to originate from pericytes or modified perivascular cells. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum histologic findings growth pattern. In contrast, solitary fibrous tumor (previously termed hemangiopericytoma) was once hypothesized have pericytic differentiation. Methods. Here, we systematically examine pericyte...
Abstract Transmembrane (TM) domains as simple a single span can perform complex biological functions using entirely lipid-embedded chemical features. Computational design has the potential to generate custom tool molecules directly targeting membrane proteins at their functional TM regions. Thus far, designed domain-targeting agents have been limited mimicking binding modes and motifs of natural interaction partners. Here, we demonstrate de novo erythropoietin receptor (EpoR) domain in...
Computationally designed transmembrane α-helical peptides (CHAMP) have been used to compete for helix–helix interactions within the membrane, enabling ability probe activation of integrins αIIbβ3 and αvβ3. Here, this method is extended towards design CHAMP that inhibit association α5β1 (TM) domains, targeting Ala–X3–Gly motif α5. Our previous algorithm was performed alongside a new workflow implemented widely Rosetta molecular modeling suite. Peptides from each computational approach...
Significance Besides anchoring proteins in membranes, transmembrane (TM) helices facilitate the assembly of multisubunit proteins. Often, TM contain several TM–helix interaction sequences, arranged such that they cannot be simultaneously engaged. The helix β3-integrin subunit contains two different sequences it uses to interact with α-subunits, one αIIb and other αv. Because integrins have distinct biological functions, ability a single use partners likely contributes this functional...
The fluorescent reporters commonly used to visualize proteins can perturb both protein structure and function. Recently, we found that 4-cyanotryptophan (4CN-Trp), a blue amino acid, is suitable for one-photon imaging applications. Here, demonstrate its utility in two-photon fluorescence microscopy by using it image integrins on cell surfaces. Specifically, solid-phase peptide synthesis generate CHAMP peptides labeled with 4-cyanoindole (4CNI) at their N-termini (computed helical...
Membrane-peptide interactions play critical roles in many cellular and organismic functions, including protection from infection, remodeling of membranes, signaling, ion transport. Peptides interact with membranes a variety ways: some associate membrane surfaces either intrinsically disordered conformations or well-defined secondary structures. sufficient hydrophobicity can also insert vertically as transmembrane monomers, further into membrane-spanning helical bundles. Indeed, peptides...
Pericytes are contractile cells that surround the endothelium of capillaries and venules throughout body. were once thought to have a limited role in blood pressure control angiogenesis. Today, knowledge about pericytes other perivascular stem has vastly expanded. The understanding biologic significance was most changed by recognition identity mesenchymal cells. following review article will summarize known functions importance particular relevance tumor biology. These roles include: 1) as...
Significance DNA variant libraries allow unbiased analysis of sequence–function relationships. However, exhaustive combinatorial assemblies even a modest number parts produce too large to practically screen. Library size can be reduced by manually blending remove unwanted combinations, but this yields limited improvements and is difficult scale. To address challenge, we built microfluidic hybrid valve–droplet device that selectively combines assembles into predefined composition with low...
ABSTRACT Ubiquitination is an essential post-translational regulatory process that can control protein stability, localization, and activity. Ubiquitin for eukaryotic life highly conserved, varying in only 3 amino acid positions between yeast humans. However, recent deep sequencing studies S. cerevisiae indicate ubiquitin tolerant to single mutations. To resolve this paradox, we hypothesized the set of tolerated substitutions would be reduced when cultures are not grown rich media conditions...
Transmembrane (TM) domains as simple a single span can perform complex biological functions using entirely lipid-embedded chemical features. Computational design has potential to generate custom tool molecules directly targeting membrane proteins at their functional TM regions. Thus far, designed domain-targeting agents have been limited mimicking binding modes and motifs of natural interaction partners. Here, we demonstrate the de novo erythropoietin receptor (EpoR) domain in topology...
Pericytes are contractile cells that surround the endothelium of capillaries and venules throughout body. were once thought to have a limited role in blood pressure control angiogenesis. Today, knowledge about pericytes other perivascular stem has vastly expanded. The understanding biologic significance was most changed by recognition identity mesenchymal cells. following review article will summarize known functions importance particular relevance tumor biology. These roles include: 1) as...
Osteosarcomas are the most common primary malignant bone tumors. Major advances in treatment of osteosarcoma (OS) have revolutionized their clinical and surgical care. Despite these improvements, no specific targeted therapy has yet been employed for OS treatment. The present review will outline significant cytokine signaling pathways important tumor biology, including Bone morphogenetic protein (BMP), Hedgehog, Wnt pathways. Also discussed inherent challenges studying OS, diversity...
A potent class of HIV-1 broadly neutralizing antibodies (bnAbs) targets the envelope glycoprotein’s membrane proximal exposed region (MPER) through a proposed mechanism where hypervariable loops embed into lipid bilayers and engage headgroup moieties alongside epitope. We address feasibility determinant molecular features this using multi-scale modeling. All-atom simulations 4E10, PGZL1, 10E8 LN01 docked onto HIV-like membranes consistently form phospholipid complexes at key...