Real-time heterogeneity of supramolecular assembly of amyloid precursor protein is modulated by an endocytic risk factor PICALM.

Recently, the localization of amyloid precursor protein (APP) into reversible nanoscale supramolecular assembly or "nanodomains" has been highlighted as crucial towards understanding the onset of the molecular pathology of Alzheimer's disease (AD). Surface expression of APP is regulated by proteins interacting with it, controlling its retention and lateral trafficking on the synaptic membrane. Here, we evaluated the involvement of a key risk factor for AD, PICALM, as a critical regulator of nanoscale dynamics of APP.

Cryptic association of B7-2 molecules and its implication for clustering.

T-cell co-stimulation through CD28/CTLA4:B7-1/B7-2 axis is one of the extensively studied pathways that resulted in the discovery of several FDA-approved drugs for autoimmunity and cancer. However, many aspects of the signaling mechanism remain elusive, including oligomeric association and clustering of B7-2 on the cell surface. Here, we describe the structure of the IgV domain of B7-2 and its cryptic association into 1D arrays that appear to represent the pre-signaling state of B7-2 on the cell membrane.

mEosBrite Are Bright Variants of mEos3.2 Developed by Semirational Protein Engineering.

mEos3.2 is a photoconvertible fluorescence protein with comparatively low brightness, which limits its application in live Super resolution microscopy. To address this issue, we have used semi-rational protein engineering to develop mEosBrite, a new class of improved brightness variants.