The N-terminal region of the ubiquitin regulatory x (UBX) domain-containing Protein 1 (UBXD1) modulates interdomain communication within the valosin-containing Protein p97

Valosin-containing protein/p97 is an ATP-driven protein segregase that cooperates with distinct protein cofactors to control various aspects of cellular homeostasis. Mutations at the interface between the regulatory N-domain and the first of two ATPase domains (D1 and D2) deregulate the ATPase activity and cause a multisystem degenerative disorder, inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia/amyotrophic lateral sclerosis. Intriguingly, the mutations affect only a subset of p97-mediated pathways correlating with unbalanced cofactor interactions and most prominently compromised binding of the ubiquitin regulatory X domain-containing protein 1 (UBXD1) cofactor during endolysosomal sorting of caveolin-1. However, how the mutations impinge on the p97-cofactor interplay is unclear so far. In cell-based endosomal localization studies, we identified a critical role of the N-terminal region of UBXD1 (UBXD1-N). Biophysical studies using NMR and CD spectroscopy revealed that UBXD1-N can be classified as intrinsically disordered. NMR titration experiments confirmed a valosin-containing protein/p97 interaction motif and identified a second binding site at helices 1 and 2 of UBXD1-N as binding interfaces for p97. In reverse titration experiments, we identified two distant epitopes on the p97 N-domain that include disease-associated residues and an additional interaction between UBXD1-N and the D1D2 barrel of p97 that was confirmed by fluorescence anisotropy. Functionally, binding of UBXD1-N to p97 led to a reduction of ATPase activity and partial protection from proteolysis. These findings indicate that UBXD1-N intercalates into the p97-ND1 interface, thereby modulating interdomain communication of p97 domains and its activity with relevance for disease pathogenesis. We propose that the polyvalent binding mode characterized for UBXD1-N is a more general principle that defines a subset of p97 cofactors

Magnetism and morphology of Co nanocluster superlattices on GdAu2 /Au(111)- (13×13)

Under the terms of the Creative Commons Attribution License 3.0 (CC-BY).-- et al.We present a comprehensive study of the magnetism and morphology of an ultrahigh density array of Co nanoclusters self-assembled on the single atomic layer GdAu2 on Au(111) template surface. Combining scanning tunneling microscopy, x-ray magnetic circular dichroism, and magneto-optical Kerr effect measurements, we reveal a significant enhancement of the perpendicular magnetic anisotropy energy for noncoalesced single atomic layer nanoclusters compared to Co/Au(111). For coverages well beyond the onset of coalescence, we observe room-temperature in-plane magnetic remanence.We acknowledge funding from the Swiss National Science Foundation, from the Sino-Swiss Science and Technology Cooperation Project No. IZLCZ2 123892, from the Spanish Ministerio de Ciencia e Innovacion (MAT2010-21156-C03-03), from the Gipuzkoako Foru Aldundia, from the European Social Fund within the program JAE-Doc, the Basque Government (IT-621-13 and IT-627-13) and SAIOTEK (S-PE12UN095), as well as from the EU Calipso program for synchrotron access funding. The MBE chamber on DEIMOS was funded by the Agence National de la Recherche with Grant No. ANR-05-NANO-073.Peer Reviewe

Covalent assembly of a two-dimensional molecular ‘‘sponge’’ on a Cu(111) surface:Confined electronic surface states in open and closed pores

We present a new class of on-surface covalent reactions, formed between diborylene-3,4,9,10-tetraaminoperylene and trimesic acid on Cu(111), which gives rise to a porous 2D-'sponge'. This aperiodic network allowed the investigation of the dependence of electron confinement effects upon pore size, shape and even in partial confinement

STM fingerprint of molecule–adatom interactions in a self-assembled metal–organic surface coordination network on Cu(111)

7 páginas, 5 figuras, 3 tablas.-- El pdf del artículo es la versión pre-print.A novel approach of identifying metal atoms within a metal–organic surface coordination network using scanning tunnelling microscopy (STM) is presented. The Cu adatoms coordinated in the porous surface network of 1,3,8,10-tetraazaperopyrene (TAPP) molecules on a Cu(111) surface give rise to a characteristic electronic resonance in STM experiments. Using density functional theory calculations, we provide strong evidence that this resonance is a fingerprint of the interaction between the molecules and the Cu adatoms. We also show that the bonding of the Cu adatoms to the organic exodentate ligands is characterised by both the mixing of the nitrogen lone-pair orbitals of TAPP with states on the Cu adatoms and the partial filling of the lowest unoccupied molecular orbital (LUMO) of the TAPP molecule. Furthermore, the key interactions determining the surface unit cell of the network are discussed.This work was financially supported by the European Union through the Marie Curie Research Training Network PRAIRIES (MRTN-CT-2006-035810). Support from the Swiss National Science Foundation, the National Center of Competence in Research (NCCR) ‘‘Nanoscale Science’’ and the Wolfermann Naegeli Stiftung is also acknowledged. MP is also grateful for support from the Swedish Research Council (VR).Peer reviewe

Self-assembly of bicomponent molecular monolayers: Adsorption height changes and their consequences

Under the terms of the Creative Commons Attribution License 3.0 (CC-BY).-- et al.Codeposition of two molecular species [copper phtalocyanine (CuPc, donor) and perfluoropentacene (PFP, acceptor)] on noble metal (111) surfaces leads to the self-assembly of an ordered mixed layer with a maximized donor-acceptor contact area. The main driving force behind this arrangement is assumed to be the intermolecular C-Hâ̄F hydrogen-bond interactions. Such interactions would be maximized for a coplanar molecular arrangement. However, precise measurement of molecule-substrate distances in the molecular mixture reveals significantly larger adsorption heights for PFP than for CuPc. Most surprisingly, instead of leveling to increase hydrogen-bond interactions, the height difference is enhanced in the blends as compared to the heights found in single-component CuPc and PFP layers. The increased height of PFP in mixed layers points to an overall reduced interaction with the underlying substrate, and its influence on electronic properties like the interface dipole is investigated through work function measurements. © 2014 American Physical Society.This work was supported by the Spanish Grants No. MAT2010-21156-C03-01 and-C03-03, as well as No. PIB2010US-00652, and by the Basque Government (Grant No. IT-621-13). D. G. O. acknowledges support from the European Union under Grant No. FP7-PEOPLE-2010-IOF-271909. We acknowledge funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant No. 226716.Peer Reviewe

Pin1 and neurodegeneration: a new player for prion disorders?

Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders

On-Surface Covalent Linking of Organic Building Blocks on a Bulk Insulator

Kittelmann M, Rahe P, Nimmrich M, Hauke CM, Gourdon A, Kühnle A. On-Surface Covalent Linking of Organic Building Blocks on a Bulk Insulator. ACS Nano. 2011;5(10):8420-8425.On-surface synthesis in ultrahigh vacuum provides a promising strategy for creating thermally and chemically stable molecular structures at surfaces. The two-dimensional confinement of the educts, the possibility of working at higher (or lower) temperatures in the absence of solvent, and the templating effect of the surface bear the potential of preparing compounds that cannot be obtained in solution. Moreover, covalently linked conjugated molecules allow for efficient electron transport and are, thus, particularly interesting for future molecular electronics applications. When having these applications in mind, electrically insulating substrates are mandatory to provide sufficient decoupling of the molecular structure from the substrate surface. So far, however, on-surface synthesis has been achieved only on metallic substrates. Here we demonstrate the covalent linking of organic molecules on a bulk insulator, namely, calcite. We deliberately employ the strong electrostatic interaction between the carboxylate groups of halide-substituted benzoic adds and the surface calcium cations to prevent molecular desorption and to reach homolytic cleavage temperatures. This allows for the formation of aryl radicals and intermolecular coupling. By varying the number and position of the halide substitution, we rationally design the resulting structures, revealing straight lines, zigzag structures, and dimers, thus providing clear evidence for the covalent linking. Our results constitute an important step toward exploiting on-surface synthesis for molecular electronics and optics applications, which require electrically insulating rather than metallic supporting substrates

Manipulating the Conformation of Single Organometallic Chains on Au(111)

The conformations of organometallic polymers formed via the bottom-up assembly of monomer units on a metal surface are investigated, and the relationship between the adsorption geometry of the individual monomer units, the conformational structure of the chain, and the overall shape of the polymer is explored. Iodine-functionalized monomer units deposited on a Au(111) substrate are found to form linear chain structures in which each monomer is linked to its neighbors via a Au adatom. Lateral manipulation of the linear chains using a scanning tunneling microscope allows the structure of the chain to be converted from a linear to a curved geometry, and it is shown that a transformation of the overall shape of the chain is coupled to a conformational rearrangement of the chain structure as well as a change in the adsorption geometry of the monomer units within the chain. The observed conformational structure of the curved chain is well-ordered and distinct from that of the linear chains. The structures of both the linear and curved chains are investigated by a combination of scanning tunneling microscopy measurements and theoretical calculations