CRISPR-Cas constitutes a prokaryotic adaptive immune system against invading genetic elements. The crRNA and Cas protein(s) form effector complex that degrades invading nucleic acid complementary to the crRNA guide. The type III-B Cmr effector complex comprises six Cas proteins and a crRNA, and degrades RNA target. The crystal structure of the Cmr complex bound to a target analog was determined. The complex recognizes the crRNA 5ʼ-tag and deforms the guide-target duplex at 6-nt intervals. The structure reveals the periodic RNA cleavage mechanism by the Cmr complex, and provides insights into the evolution of the type I and III effector complexes.
ULK complex is the most upstream factor to initiate autophagy in higher eukaryotes. Atg101 is an essential component of the complex, but is absent from the functionally equivalent Atg1 complex in budding yeast. To elucidate the molecular functions of Atg101, we have determined the crystal structure of Atg101 complexed with Atg13. The structure reveals that Atg101 is a member of the HORMA family protein and is structurally similar to Atg13. Structure-based mutational studies reveal that Atg101 has at least two critical functions in autophagy: one is to stabilize Atg13 and the other is to recruit downstream Atg factors to autophagosome formation site.
A giant single-pass trans-membrane receptor, sorLA constructed by over 2,000 amino acid residues has been recognized as a major risk factor for Alzheimerʼs disease (AD) based on reports that its level was reduced in the brains of patients with sporadic AD, and that the increased level of amyloid-β (Aβ), the most major AD causative substance, was observed in the sorLA knockout mice. SorLA can be classified in the low-density lipoprotein receptor (LDLR) family by its domain composition, meanwhile sorLA has a unique Vps10p domain on its N-terminus unlike other LDLR family members. Last year, we discovered that sorLA Vps10p domain specifically recognizes Aβ peptide in our sorLA structural study project, and suggested that sorLA has the function to captures the newly produced Aβ peptide at endosome and dump it to lysosome using its Vps10p domain. Following the discovery, we successfully revealed the crystal structure of sorLA Vps1-p domain for its ligand free form and complexed forms with two kinds of ligand peptides, its own propetide and Aβ peptide fragments. Based on these results combined with biological experiments, we suggested that sorLA Vps10p domain can ʻspecificallyʼ recognize β-aggregation tendency.
Oxidation and reduction of the surfaces of Pt nanoparticles were observed at atomic-scale by aberration-corrected environmental transmission electron microscopy (ETEM). The surfaces of Pt nanoparticles supported on CeO2 were gradually oxidized in O2 during ETEM observation at room temperature. The surface Pt oxides were promptly reduced to Pt in a vacuum or by adding a small amount of CO or H2O vapor to dominant O2. This study provides insights at atomic-scale into the oxidation and reduction process of the surfaces of Pt nanoparticles that are exposed to activated gases.
Hydrogen is known as an ultimate clean energy source and is thus discussed as a future sustainable energy carrier. Hydrogenases catalyze the reversible oxidation of the molecular hydrogen. We report the crystal structure analysis of [NiFe] hydrogenase from sulfate reducer at subatomic resolution. The structure reveals that the hydride bridge between nickel and iron at the active site and the possible proton bound site at the cysteine residue, resulting from the initial heterolytic splitting of dihydrogen by the enzyme. This finally clarifies the initial step in the mechanism of hydrogen conversion.