AAA+ proteolytic machines unfold proteins before degrading them. Here, we present cryoEM structures of ClpXP-substrate complexes that reveal a postulated but heretofore unseen intermediate in substrate unfolding/degradation. A ClpX hexamer draws natively folded substrates tightly against its axial channel via interactions with a fused C-terminal degron tail and ClpX-RKH loops that flexibly conform to the globular substrate.
View Article and Find Full Text PDFHuman cellular retinol binding protein II (hCRBPII) was used as a protein engineering platform to rationally regulate absorptive and emissive properties of a covalently bound fluorogenic dye. We demonstrate the binding of a thio-dapoxyl analog via formation of a protonated imine between an active site lysine residue and the chromophore's aldehyde. Rational manipulation of the electrostatics of the binding pocket results in a 204 nm shift in absorption and a 131 nm shift in emission.
View Article and Find Full Text PDFBackground: Prenatal and postnatal depression (PND) is associated with adverse outcomes for mother, fetus, and child. The aim of study was to examine the prevalence and risk factors of prenatal and postnatal depressive symptoms.
Materials And Methods: This was a cross-sectional and hospital-based survey of 2305 pregnant women and post-partum women (18-48 years) that was registered in the Babol Pregnancy Mental Health Registry (BPMHR) database from June 2020 to March 2021.
The primary hurdles for small interference RNA (siRNA) in clinical use are targeted and cytosolic delivery. To overcome both challenges, we have established a novel platform based on phage display, called NNJA. In this approach, a lysosomal cathepsin substrate is engineered within the flexible loops of PIII, that is displaying a unique random sequence at its N-terminus.
View Article and Find Full Text PDF