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10 p.-6 fig. ; Hsp70 chaperones comprise two domains, the nucleotide-binding domain (Hsp70NBD), responsible for structural and functional changes in the chaperone, and the substrate-binding domain (Hsp70SBD), involved in substrate interaction. Substrate binding and release in Hsp70 is controlled by the nucleotide state of DnaKNBD, with ATP inducing the open, substrate-receptive DnaKSBD conformation, whereas ADP forces its closure. DnaK cycles between the two conformations through interaction with two cofactors, the Hsp40 co-chaperones (DnaJ in Escherichia coli) induce the ADP state, and the nucleotide exchange factors (GrpE in E. coli) induce the ATP state. X-ray crystallography showed that the GrpE dimer is a nucleotide exchange factor that works by interaction of one of its monomers with DnaKNBD. DnaKSBD location in this complex is debated; there is evidence that it interacts with the GrpE N-terminal disordered region, far from DnaKNBD. Although we confirmed this interaction using biochemical and biophysical techniques, our EM-based three-dimensional reconstruction of the DnaK-GrpE complex located DnaKSBD near DnaKNBD. This apparent discrepancy between the functional and structural results is explained by our finding that the tail region of the GrpE dimer in the DnaK-GrpE complex bends and its tip contacts DnaKSBD, whereas the DnaKNBD-DnaKSBD linker contacts the GrpE helical region. We suggest that these interactions define a more complex role for GrpE in the control of DnaK function. ; This work was supported in part by Spanish Ministry of Economy and Innovation Grants BFU2013-44202 (to J. M. V.), SAF2011-22988 (to O. L.), and BFU2013-47059 (to A. M.), Madrid Regional Government Grants S2013/MIT-2807 (to J. M. V.) and S2010/BMD-2316 (to O. L.), and Basque Government Grant IT709-13 (to A. M.). ; Peer reviewed

(Figure Presented) The formation and full characterization of single self-assembling α,γ-peptide nanotubes (α,γ-SPNs) is described. The introduction of C60 into cyclic peptides allows the preparation of supramolecular 1D fullerene arrangements induced by peptide nanotube formation under appropriate conditions. © 2009 American Chemical Society. ; This work was supported by the Spanish Ministry of Education and Science and the ERDF [SAF2007-61015 and Consolider Ingenio 2010 (CSD2007-00006)] and the Xunta de Galicia (GRC2006/ 132, PGIDIT06PXIB209018PR, PGIDIT08CSA047209PR, and R2006/ 124). The work by J.M.V. and J.L.C. was supported by Grants BFU2007- 62382/BMC from the Spanish MEC (J.M.V.) and S-0505/MAT/0283 from the Madrid Regional Government (J.M.V. and J.L.C.). C.R. and R.J.B. thank the Spanish MEC for their FPU Fellowships. We also thank Dr. Carmen Serra (Nanotechnology and Surface Analysis Service at C.A.C.T.I., University of Vigo) for her help with STM. We also thank Dowpharma for their kind gift of ENZA enzymes used in the preparation of D-Boc-γ-Acp-OH. ; Peer reviewed

This is the author accepted manuscript. The final version is avialble via PNAS at http://www.pnas.org/content/112/16/E1994.long#ack-1. ; We describe the isolation and detailed structural characterization of stable toxic oligomers of α-synuclein that have accumulated during the process of amyloid formation. Our approach has allowed us to identify distinct subgroups of oligomers and to probe their molecular architectures by using cryo-electron microscopy (cryoEM) image reconstruction techniques. Although the oligomers exist in a range of sizes, with different extents and nature of β-sheet content and exposed hydrophobicity, they all possess a hollow cylindrical architecture with similarities to certain types of amyloid fibril, suggesting that the accumulation of at least some forms of amyloid oligomers is likely to be a consequence of very slow rates of rearrangement of their β-sheet structures. Our findings reveal the inherent multiplicity of the process of protein misfolding and the key role the β-sheet geometry acquired in the early stages of the self-assembly process plays in dictating the kinetic stability and the pathological nature of individual oligomeric species. ; We thank Dr. Katherine Stott, from the Biophysics Facility, Department of Biochemistry, University of Cambridge, for her assistance in using these facilities. This work was supported by the Agency for Science, Technology and Research, Singapore (S.W.C.), the "La Caixa" foundation (S.D.), Wellcome/MRC (Medical Research Council) Parkinson's Disease Consortium Grant WT089698 (to E.D. and N.W.W.), National Institute for Health Research Biomedical Research Centres funding at University College London (to N.W.W.), the BBSRC through Grants BB/H003843/1 (to M.O.) and BB/E019927/1 (to C.M.D.), the Spanish Ministry of Economy and Competitiveness through Grants SAF 2012-39720 (to C.R.), BFU2013-44202 (to J.M.V.), and BIO2011-28941-C03-03 (to C.A. and G.R.), the Spanish Ministry of Health with cofunding by The European Regional Development Fund through Grant CP10/00527 (to C.R.), the Madrid Regional Government through Grant S2013/MIT-2807 (to J.M.V.), Parkinson's UK through Grant H-0903 (to T.G.), the Wellcome Trust, the Leverhulme Trust, the European Commission through project LSHM-CT-2006-037525 (to C.M.D.), the Medical Research Council through Grant MRC G1002272 (to E.J.D.-G. and C.M.D.), and the Engineering and Physical Sciences Research Council (C.M.D.). A.Y.A. was a Parkinson's UK Senior Research Fellow. N.C. is a Royal Society Research Fellow and also acknowledges financial support by the Human Frontier Science Program from Long-Term Fellowship LT000795/2009.