The PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.

ASAP1 is a multidomain Arf GTPase-activating protein (ArfGAP) that catalyzes GTP hydrolysis on the small GTPase Arf1 and is implicated in cancer progression. The PH domain of ASAP1 enhances its activity greater than 7 orders of magnitude but the underlying mechanisms remain poorly understood. Here, we combined Nuclear Magnetic Resonance (NMR), Molecular Dynamic (MD) simulations and mathematical modeling of functional data to build a comprehensive structural-mechanistic model of the complex of Arf1 and the ASAP1 PH domain on a membrane surface.

Pre-implementation planning to enhance integration of HIV and behavioral health care services at two Ryan White-funded HIV care centers.

Behavioral health conditions are disproportionately experienced by people living with Human immunodeficiency virus (HIV), including young Black gay, bisexual, and other men who have sex with men (GBMSM). Left unaddressed, these symptoms can adversely impact HIV care outcomes. Improving the integration of behavioral health and HIV care services has been proposed as a strategy to address this challenge.

CD28 hinge used in chimeric antigen receptor (CAR) T-cells exhibits local structure and conformational exchange amidst global disorder.

T-cell therapies based on chimeric antigen receptor (CAR) targeting of a tumor-specific antigen offer hope for patients with relapsed or refractory cancers. CAR hinge and transmembrane regions link antigen recognition domains to intracellular signal transduction domains. Here, we apply biophysical methods to characterize the structure and dynamic properties of the CD28 CAR hinge (CD28H) used in an FDA-approved CD19 CAR for the treatment of B-lineage leukemia/lymphoma.

Existence of Singularities in NMR Relaxation Dispersion Profiles: Implications for Hidden Dynamics.

It is common for NMR relaxation dispersion experiments to suggest an absence of dynamics despite anecdotal indications of conformational dynamics. We explore the potential explanations and approaches to this conundrum. Some inconsistencies have been observed between two relaxation dispersion experiments, Carr-Purcell-Meiboom-Gill (CPMG) and adiabatic relaxation dispersion experiments, in recent dynamic studies of different biomolecules.