Probing conformational dynamics of an enzymatic active site by an in situ single fluorogenic probe under piconewton force manipulation.
AuthorsPal N, Wu M, Lu HP
JournalProc Natl Acad Sci U S A
PubMed ID27940917
'Unraveling the conformational details of an enzyme during the essential steps of a catalytic reaction (i.e., enzyme-substrate interaction, enzyme-substrate active complex formation, nascent product formation, and product release) is challenging due to the transient nature of intermediate conformational states, conformational fluctuations, and the associated complex dynamics. Here we report our ... More
AuthorsBulley S, Fernández-Peña C, Hasan R, Leo MD, Muralidharan P, Mackay CE, Evanson KW, Moreira-Junior L, Mata-Daboin A, Burris SK, Wang Q, Kuruvilla KP, Jaggar JH
JournalElife
PubMed ID30511640
'Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth ... More
Endothelin-1 Stimulates Vasoconstriction Through Rab11A Serine 177 Phosphorylation.
AuthorsZhai X, Leo MD, Jaggar JH
JournalCirc Res
PubMed ID28696251
Large-conductance calcium-activated potassium channels (BK) are composed of pore-forming BKa and auxiliary ß1 subunits in arterial smooth muscle cells (myocytes). Vasoconstrictors, including endothelin-1 (ET-1), inhibit myocyte BK channels, leading to contraction, but mechanisms involved are unclear. Recent evidence indicates that BKa is primarily plasma membrane localized, whereas the cellular location ... More
Impaired Trafficking of ß1 Subunits Inhibits BK Channels in Cerebral Arteries of Hypertensive Rats.
AuthorsLeo MD, Zhai X, Yin W, Jaggar JH
JournalHypertension
PubMed ID30012867
Hypertension is a risk factor for cerebrovascular diseases, including stroke and dementia. During hypertension, arteries become constricted and are less responsive to vasodilators, including nitric oxide (NO). The regulation of arterial contractility by smooth muscle cell (myocyte) large-conductance calcium (Ca ... More
Ca
AuthorsChowdhury D, Turner M, Patriarchi T, Hergarden AC, Anderson D, Zhang Y, Sun J, Chen CY, Ames JB, Hell JW
JournalEMBO J
PubMed ID29118000
Postsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca ... More
A toolbox of anti-mouse and anti-rabbit IgG secondary nanobodies.
AuthorsPleiner T, Bates M, Görlich D
JournalJ Cell Biol
PubMed ID29263082
Polyclonal anti-immunoglobulin G (anti-IgG) secondary antibodies are essential tools for many molecular biology techniques and diagnostic tests. Their animal-based production is, however, a major ethical problem. Here, we introduce a sustainable alternative, namely nanobodies against all mouse IgG subclasses and rabbit IgG. They can be produced at large scale in ... More
The Increased Endogenous Sulfur Dioxide Acts as a Compensatory Mechanism for the Downregulated Endogenous Hydrogen Sulfide Pathway in the Endothelial Cell Inflammation.
AuthorsZhang D, Wang X, Tian X, Zhang L, Yang G, Tao Y, Liang C, Li K, Yu X, Tang X, Tang C, Zhou J, Kong W, Du J, Huang Y, Jin H
JournalFront Immunol
PubMed ID29760703
Endogenous hydrogen sulfide (H
Omomyc Reveals New Mechanisms To Inhibit the MYC Oncogene.
AuthorsDemma MJ, Mapelli C, Sun A, Bodea S, Ruprecht B, Javaid S, Wiswell D, Muise E, Chen S, Zelina J, Orvieto F, Santoprete A, Altezza S, Tucci F, Escandon E, Hall B, Ray K, Walji A, O'Neil J
JournalMol Cell Biol
PubMed ID31501275
The MYC oncogene is upregulated in human cancers by translocation, amplification, and mutation of cellular pathways that regulate Myc. Myc/Max heterodimers bind to E box sequences in the promoter regions of genes and activate transcription. The MYC inhibitor Omomyc can reduce the ability of MYC to bind specific box sequences ... More