Mark Yeager
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View article: Mechanism of Phosphatidylserine Lipid Scrambling by Human SERINC3, an HIV-1 Restriction Factor
Mechanism of Phosphatidylserine Lipid Scrambling by Human SERINC3, an HIV-1 Restriction Factor Open
The HIV-1 restriction factor, hSERINC3, functions as a lipid scramblase, translocating lipids across the bilayer in reconstituted proteoliposomes and the viral envelope. Phosphatidylserine(PS) scrambling and exposure at the outer leaflet a…
View article: Kinetic implications of IP <sub>6</sub> anion binding on the molecular switch of HIV-1 capsid assembly
Kinetic implications of IP <sub>6</sub> anion binding on the molecular switch of HIV-1 capsid assembly Open
HIV-1 capsid (CA) proteins self-assemble into a fullerene-shaped CA, enabling cellular transport and nuclear entry of the viral genome. A structural switch comprising the Thr-Val-Gly- Gly (TVGG) motif either assumes a disordered coil or a …
View article: Kinetic Implications of IP<sub>6</sub>Anion Binding on the Molecular Switch of the HIV-1 Capsid Assembly
Kinetic Implications of IP<sub>6</sub>Anion Binding on the Molecular Switch of the HIV-1 Capsid Assembly Open
HIV-1 capsid proteins (CA) self-assemble into a fullerene-shaped capsid, enabling cellular transport and nuclear entry of the viral genome. A structural switch comprising the Thr-Val-Gly-Gly (TVGG) motif either assumes a disordered coil or…
View article: Platelet integrin αIIbβ3 plays a key role in venous thrombogenesis in a mouse model
Platelet integrin αIIbβ3 plays a key role in venous thrombogenesis in a mouse model Open
Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. Previous studies have shown that the accumulation of platelets and neutrophils at sites of endothelial cell activation is a pr…
View article: Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures
Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures Open
Connexins (Cxs) are a family of integral membrane proteins, which function as both hexameric hemichannels (HCs) and dodecameric gap junction channels (GJCs), behaving as conduits for the electrical and molecular communication between cells…
View article: G protein beta4 as a structural determinant of enhancednucleotide exchange in the A2A adenosine receptor Gs complex
G protein beta4 as a structural determinant of enhancednucleotide exchange in the A2A adenosine receptor Gs complex Open
Adenosine A2A receptors (A2AAR) evoke pleiotropic intracellular signaling events via activation of the stimulatory heterotrimeric G protein, Gs. Here, we used cryoEM to solve the agonist-bound structure of A2AAR in a complex with full-leng…
View article: Cryo-EM structures of full-length integrin αIIbβ3 in native lipids
Cryo-EM structures of full-length integrin αIIbβ3 in native lipids Open
Platelet integrin αIIbβ3 is maintained in a bent inactive state (low affinity to physiologic ligand), but can rapidly switch to a ligand-competent (high-affinity) state in response to intracellular signals (“inside-out” activation). Once b…
View article: Inositol Hexakisphosphate (IP6) Accelerates Immature HIV-1 Gag Protein Assembly toward Kinetically Trapped Morphologies
Inositol Hexakisphosphate (IP6) Accelerates Immature HIV-1 Gag Protein Assembly toward Kinetically Trapped Morphologies Open
During the late stages of the HIV-1 lifecycle, immature virions are produced by the concerted activity of Gag polyproteins, primarily mediated by the capsid (CA) and spacer peptide 1 (SP1) domains, which assemble into a spherical lattice, …
View article: Inositol hexakisphosphate (IP6) accelerates immature HIV-1 Gag protein assembly towards kinetically-trapped morphologies
Inositol hexakisphosphate (IP6) accelerates immature HIV-1 Gag protein assembly towards kinetically-trapped morphologies Open
During the late stages of the HIV-1 lifecycle, immature virions are produced by the concerted activity of Gag polyproteins, primarily mediated by the capsid (CA) and spacer peptide 1 (SP1) domains, which assemble into a spherical lattice, …
View article: Preservation of HIV-1 Gag Helical Bundle Symmetry by Bevirimat Is Central to Maturation Inhibition
Preservation of HIV-1 Gag Helical Bundle Symmetry by Bevirimat Is Central to Maturation Inhibition Open
The assembly and maturation of human immunodeficiency virus type 1 (HIV-1) require proteolytic cleavage of the Gag polyprotein. The rate-limiting step resides at the junction between the capsid protein CA and spacer peptide 1, which assemb…
View article: Preservation of HIV-1 Gag helical bundle symmetry by bevirimat is central to maturation inhibition
Preservation of HIV-1 Gag helical bundle symmetry by bevirimat is central to maturation inhibition Open
The assembly and maturation of human immunodeficiency virus type-1 (HIV-1) requires proteolytic cleavage of the Gag polyprotein. The rate-limiting step resides at the junction between the capsid protein CA and spacer peptide 1, which assem…
View article: ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels
ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels Open
Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, th…
View article: A Constitutively Closed Pannexin1 Channel in Lipid Bilayer Nanodiscs Assembles as a Large-Pore Heptamer
A Constitutively Closed Pannexin1 Channel in Lipid Bilayer Nanodiscs Assembles as a Large-Pore Heptamer Open
SUMMARY Pannexin 1 (Panx1) channels are widely expressed and play important roles in apoptotic cell clearance, inflammation, blood pressure regulation, neurological disorders, opiate withdrawal, and cancer progression and metastasis. We pe…
View article: Synthetic antibodies against BRIL as universal fiducial marks for single−particle cryoEM structure determination of membrane proteins
Synthetic antibodies against BRIL as universal fiducial marks for single−particle cryoEM structure determination of membrane proteins Open
We propose the concept of universal fiducials based on a set of pre-made semi-synthetic antibodies (sABs) generated by customized phage display selections against the fusion protein BRIL, an engineered variant of apocytochrome b562a. These…
View article: Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation
Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation Open
Many members of the AAA+ ATPase family function as hexamers that unfold their protein substrates. These AAA unfoldases include spastin, which plays a critical role in the architecture of eukaryotic cells by driving the remodeling and sever…
View article: Constitutive SRC-mediated phosphorylation of pannexin 1 at tyrosine 198 occurs at the plasma membrane
Constitutive SRC-mediated phosphorylation of pannexin 1 at tyrosine 198 occurs at the plasma membrane Open
Pannexin 1 (PANX1)-mediated ATP release in vascular smooth muscle coordinates α1-adrenergic receptor (α1-AR) vasoconstriction and blood pressure homeostasis. We recently identified amino acids 198-200 (YLK) on the PANX1 intracellular loop …
View article: MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat
MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat Open
HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to…
View article: MicroED Structures of HIV-1 Gag CTD-SP1 Reveal Binding Interactions with the Maturation Inhibitor Bevirimat
MicroED Structures of HIV-1 Gag CTD-SP1 Reveal Binding Interactions with the Maturation Inhibitor Bevirimat Open
HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to…
View article: Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane
Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane Open
Significance In order for HIV to proliferate, viral proteins and genomic dimers are assembled at host cell membranes and released as immature virions. Disrupting this key intermediate step in viral replication is a potential target for tre…
View article: Immature HIV-1 Lattice Assembly Dynamics are Regulated by Scaffolding from Nucleic Acid and the Plasma Membrane
Immature HIV-1 Lattice Assembly Dynamics are Regulated by Scaffolding from Nucleic Acid and the Plasma Membrane Open
The packaging and budding of Gag polyprotein and viral ribonucleic acid (RNA) is a critical step in the human immunodeficiency virus-1 (HIV-1) lifecycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) …