Assessment of the percentage of full recombinant adeno-associated virus particles in a gene therapy drug using CryoTEM.

In spite of continuous development of gene therapy vectors with thousands of drug candidates in clinical drug trials there are only a small number approved on the market today stressing the need to have characterization methods to assist in the validation of the drug development process. The level of packaging of the vector capsids appears to play a critical role in immunogenicity, hence an objective quantitative method assessing the content of particles containing a genome is an essential quality measurement. As transmission electron microscopy (TEM) allows direct visualization of the particles present in a specimen, it naturally seems as the most intuitive method of choice for characterizing recombinant adeno-associated virus (rAAV) particle packaging.

Towards structural and functional characterization of photosynthetic and mitochondrial supercomplexes.

Bioenergetic reactions in chloroplasts and mitochondria are catalyzed by large multi-subunit membrane proteins. About two decades ago it became clear that several of these large membrane proteins further associate into supercomplexes and since then a number of new ones have been described. In this review we focus on supercomplexes involved in light harvesting and electron transfer in the primary reactions of oxygenic photosynthesis and on the mitochondrial supercomplexes that catalyze electron transfer and ATP synthesis in oxidative phosphorylation.

Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states.

Ionotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory signaling in the nervous system. Despite the profound importance of iGluRs to neurotransmission, little is known about the structures and dynamics of intact receptors in distinct functional states. Here, we elucidate the structures of the intact GluA2 AMPA receptor in an apo resting/closed state, in an activated/pre-open state bound with partial agonists and a positive allosteric modulator, and in a desensitized/closed state in complex with fluorowilliardiine.

Focus on membrane differentiation and membrane domains in the prokaryotic cell.

A summary is presented of membrane differentiation in the prokaryotic cell, with an emphasis on the organization of proteins in the plasma/cell membrane. Many species belonging to the Eubacteria and Archaea have special membrane domains and/or membrane proliferation, which are vital for different cellular processes. Typical membrane domains are found in bacteria where a specific membrane protein is abundantly expressed.

A novel photosynthetic strategy for adaptation to low-iron aquatic environments.

Iron (Fe) availability is a major limiting factor for primary production in aquatic environments. Cyanobacteria respond to Fe deficiency by derepressing the isiAB operon, which encodes the antenna protein IsiA and flavodoxin. At nanomolar Fe concentrations, a PSI-IsiA supercomplex forms, comprising a PSI trimer encircled by two complete IsiA rings.