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Structural basis for amyloidogenic peptide recognition by ​sorLA

SorLA is a neuronal sorting receptor considered to be a major risk factor for Alzheimer’s disease. We have recently reported that it directs lysosomal targeting of nascent neurotoxic ​amyloid-β (​) peptides by directly binding ​. Here, we determined the crystal structure of the human ​sorLA domain responsible for ​ capture, Vps10p, in an unbound state and in complex with two ligands. Vps10p assumes a ten-bladed β-propeller fold with a large tunnel at the center. An internal ligand derived from the ​sorLA propeptide bound inside the tunnel to extend the β-sheet of one of the propeller blades. The structure of the ​sorLA Vps10p-​ complex revealed that the same site is used. Peptides are recognized by ​sorLA Vps10p in redundant modes without strict dependence on a particular amino acid sequence, thus suggesting a broad specificity toward peptides with a propensity for β-sheet formation.

Agreement on Academic Exchange between IPR and College of Physical and Mathematical Science, the Australian National University

IPR concluded an academic exchange agreement with College of Physical and Mathematical Science, Research School of Chemistry, the Australian National University on November 20, 2014. The agreement aims to enhance academic exchange and research collaboration among students and researchers between our institutes, with common goal to advance scientific research in Asia and Oceania together.

Grease matrix as a versatile carrier of proteins for serial crystallography

Femtosecond X-ray serial crystallography has revolutionized atomic resolution structural investigation by drastically expanding the accessibility to proteins in small-sized crystals, at room temperature and on dynamic reaction. Despite such an enticing opportunity, robust and reliable crystal carrying media are largely lacking. Here, we introduce a grease matrix carrier for protein microcrystals to obtain the structures of lysozyme, glucose isomerase, thaumatin and fatty acid-binding protein type-3 beyond 2Å resolution under ambient conditions.

Protein Data Bank: 100,000 structures

Wednesday May 14, 2014 00:00 UTC (Coordinated Universal Time) Spanning the globe from the US, UK, and Japan, the Worldwide Protein Data Bank (wwPDB) organization announces that the Protein Data Bank archive now contains more than 100,000 entries.

ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport

Cilia and flagella are formed and maintained by intraflagellar transport (IFT) and play important roles in sensing and moving across species. At the distal tip of the cilia/flagella, IFT complexes turn around to switch from anterograde to retrograde transport, however, the underlying regulatory mechanism is unclear. Here, we identified ICK kinase localization at the tip of cilia as a regulator of ciliary transport. In ICK-deficient mice, we found ciliary defects in neuronal progenitor cells with Hedgehog signal defects. ICK-deficient cells formed cilia with mislocalized Hedgehog signaling components. Loss of ICK caused the accumulation of IFT-A, IFT-B, and BBSome components at the ciliary tips. In contrast, overexpression of ICK induced the strong accumulation of IFT-B but not IFT-A or BBSome components at ciliary tips. In addition, ICK directly phosphorylated Kif3a, while inhibition of this Kif3a phosphorylation affected ciliary formation. Our results suggest that ICK is a Kif3a kinase and essential for proper ciliogenesis in development by regulating ciliary transport at the tip of cilia.