SorCS2 binds progranulin to regulate motor neuron development.

Motor neuron (MN) development and nerve regeneration requires orchestrated action of a vast number of molecules. Here, we identify SorCS2 as a progranulin (PGRN) receptor that is required for MN diversification and axon outgrowth in zebrafish and mice. In zebrafish, SorCS2 knockdown also affects neuromuscular junction morphology and fish motility.

Protein fibrillation from another small angle-SAXS data analysis of developing systems.

During the fibrillation process amyloid proteins undergo structural changes at very different length and time scales. Small angle X-ray scattering (SAXS) is a method that is uniquely suitable for the structural analysis of this process. Careful measures must, however, be taken both in the sample preparation, data collection and data analysis procedures to ensure proper data quality, coverage of the process and reliable interpretation.

Protein fibrillation from another small angle: Sample preparation and SAXS data collection.

Protein fibrillation associates with several chronic, progressive, and fatal disorders, counting well-known maladies as Parkinson's, Alzheimer's, and Huntington's disease. The fibrillation process includes structural changes and aggregation of the disease specific protein, resulting in a mixture of different structural states covering nm to μm scale in varying volume fractions. SAXS uniquely enables structural investigations of such evolving mixtures but requires that the underlying main data collection experiment is carefully prepared.

Identifying Biological and Biophysical Features of Different Maturation States of α-Synuclein Amyloid Fibrils.

Protein aggregates, hereunder amyloid fibrils, can undergo a maturation process, whereby early formed aggregates undergo a structural and physicochemical transition leading to more mature species. In the case of amyloid-related diseases, such maturation confers distinctive biological properties of the aggregates, which may account for a range of diverse pathological subtypes. Here, we present a protocol for the preparation of α-synuclein amyloid fibrils differing in the level of their maturation.

Structure and thermodynamics of transient protein-protein complexes by chemometric decomposition of SAXS datasets.

Transient biomolecular interactions play crucial roles in many cellular signaling and regulation processes. However, deciphering the structure of these assemblies is challenging owing to the difficulties in isolating complexes from the individual partners. The additive nature of small-angle X-ray scattering (SAXS) data allows for probing the species present in these mixtures, but decomposition into structural and thermodynamic information is difficult.