Dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin

Throughout evolution, one of the most ancient forms of aggression between cells or organisms has been the production of proteins or peptides affecting the permeability of the target cell membrane. This class of virulence factors includes the largest family of bacterial toxins, the pore-forming toxins (PFTs). PFTs are bistable structures that can exist in a soluble and a transmembrane state. It is unclear what drives biosynthetic folding towards the soluble state, a requirement that is essential to protect the PFT-producing cell. Here we have investigated the folding of aerolysin, produced by the human pathogen Aeromonas hydrophila, and more specifically the role of the C-terminal propeptide (CTP). By combining the predictive power of computational techniques with experimental validation using both structural and functional approaches, we show that the CTP prevents aggregation during biosynthetic folding. We identified specific residues that mediate binding of the CTP to the toxin. We show that the CTP is crucial for the control of the aerolysin activity, since it protects individual subunits from aggregation within the bacterium and later controls assembly of the quaternary pore-forming complex at the surface of the target host cell. The CTP is the first example of a C-terminal chain-linked chaperone with dual function

Some aspects of the venom proteome of the Colubridae snake Philodryas olfersii revealed from a Duvernoy’s (venom) gland transcriptome

AbstractWe investigated the putative toxins of Philodryas olfersii (Colubridae), a representative of a family of snakes neglected in venom studies despite their growing medical importance. Transcriptomic data of the venom gland complemented by proteomic analysis of the gland secretion revealed the presence of major toxin classes from the Viperidae family, including serine proteases, metalloproteases, C-type lectins, Crisps, and a C-type natriuretic peptide (CNP). Interestingly, the phylogenetic analysis of the CNP precursor showed it as a linker between two related precursors found in Viperidae and Elapidae snakes. We suggest that these precursors constitute a monophyletic group derived from the vertebrate CNPs

Structure and dynamics of Rh surfaces

Lattice relaxations, surface phonon spectra, surface energies, and work functions are calculated for Rh(100) and Rh(110) surfaces using density-functional theory and the full-potential linearized augmented plane wave method. Both, the local-density approximation and the generalized gradient approximation to the exchange-correlation functional are considered. The force constants are obtained from the directly calculated atomic forces, and the temperature dependence of the surface relaxation is evaluated by minimizing the free energy of the system. The anharmonicity of the atomic vibrations is taken into account within the quasiharmonic approximation. The importance of contributions from different phonons to the surface relaxation is analyzed.Comment: 9 pages, 7 figures, scheduled to appear in Phys. Rev. B, Feb. 15 (1998). Other related publications can be found at http://www.rz-berlin.mpg.de/th/paper.htm

Giant Gravitons in Conformal Field Theory

Giant gravitons in AdS_5 x S^5, and its orbifolds, have a dual field theory representation as states created by chiral primary operators. We argue that these operators are not single-trace operators in the conformal field theory, but rather are determinants and subdeterminants of scalar fields; the stringy exclusion principle applies to these operators. Evidence for this identification comes from three sources: (a) topological considerations in orbifolds, (b) computation of protected correlators using free field theory and (c) a Matrix model argument. The last argument applies to AdS_7 x S^4 and the dual (2,0) theory, where we use algebraic aspects of the fuzzy 4-sphere to compute the expectation value of a giant graviton operator along the Coulomb branch of the theory.Comment: 37 pages, LaTeX, 1 figure. v2: references and acknowledgements added, small correction

A toy model for the AdS/CFT correspondence

We study the large N gauged quantum mechanics for a single Hermitian matrix in the Harmonic oscillator potential well as a toy model for the AdS/CFT correspondence. We argue that the dual geometry should be a string in two dimensions with a curvature of stringy size. Even though the dual geometry is not weakly curved, one can still gain knowledge of the system from a detailed study of the open-closed string duality. We give a mapping between the basis of states made of traces (closed strings) and the eigenvalues of the matrix (D-brane picture) in terms of Schur polynomials. We connect this model with the study of giant gravitons in AdS_5 x S^5. We show that the two giant gravitons that expand along AdS_5 and S^5 can be interpreted in the matrix model as taking an eigenvalue from the Fermi sea and exciting it very much, or as making a hole in the Fermi sea respectively. This is similar to recent studies of the c=1 string. This connection gives new insight on how to perform calculations for giant gravitons.Comment: 19 pages JHEP, 4 figures. v2: comments added, typos fixed, additional refs. v3: The paper has been largely revised, to make the relation as a limit of N=4 SYM clear, also some proofs have been written in full rather than sketched. This updated version reflects the changes that were made in the published versio

(Sub)mm Interferometry Applications in Star Formation Research

This contribution gives an overview about various applications of (sub)mm interferometry in star formation research. The topics covered are molecular outflows, accretion disks, fragmentation and chemical properties of low- and high-mass star-forming regions. A short outlook on the capabilities of ALMA is given as well.Comment: 20 pages, 7 figures, in proceedings to "2nd European School on Jets from Young Star: High Angular Resolution Observations". A high-resolution version of the paper can be found at http://www.mpia.de/homes/beuther/papers.htm

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Lysine methylation by the mitochondrial methyltransferase FAM173B optimizes the function of mitochondrial ATP synthase

Lysine methylation is an important post-translational modification that is also present on mitochondrial proteins, but the mitochondrial lysine-specific methyltransferases (KMTs) responsible for modification are in most cases unknown. Here, we set out to determine the function of human family with sequence similarity 173 member B (FAM173B), a mitochondrial methyltransferase (MTase) reported to promote chronic pain. Using bioinformatics analyses and biochemical assays, we found that FAM173B contains an atypical, noncleavable mitochondrial targeting sequence responsible for its localization to mitochondria. Interestingly, CRISPR/Cas9-mediated KO of FAM173B in mammalian cells abrogated trimethylation of Lys-43 in ATP synthase c-subunit (ATPSc), a modification previously reported as ubiquitous among metazoans. ATPSc methylation was restored by complementing the KO cells with enzymatically active human FAM173B or with a putative FAM173B orthologue from the nematode Caenorhabditis elegans. Interestingly, lack of Lys-43 methylation caused aberrant incorporation of ATPSc into the ATP synthase complex and resulted in decreased ATP-generating ability of the complex, as well as decreased mitochondrial respiration. In summary, we have identified FAM173B as the long-sought KMT responsible for methylation of ATPSc, a key protein in cellular ATP production, and have demonstrated functional significance of ATPSc methylation. We suggest renaming FAM173B to ATPSc-KMT (gene name ATPSCKMT)

Star Formation and Dynamics in the Galactic Centre

The centre of our Galaxy is one of the most studied and yet enigmatic places in the Universe. At a distance of about 8 kpc from our Sun, the Galactic centre (GC) is the ideal environment to study the extreme processes that take place in the vicinity of a supermassive black hole (SMBH). Despite the hostile environment, several tens of early-type stars populate the central parsec of our Galaxy. A fraction of them lie in a thin ring with mild eccentricity and inner radius ~0.04 pc, while the S-stars, i.e. the ~30 stars closest to the SMBH (<0.04 pc), have randomly oriented and highly eccentric orbits. The formation of such early-type stars has been a puzzle for a long time: molecular clouds should be tidally disrupted by the SMBH before they can fragment into stars. We review the main scenarios proposed to explain the formation and the dynamical evolution of the early-type stars in the GC. In particular, we discuss the most popular in situ scenarios (accretion disc fragmentation and molecular cloud disruption) and migration scenarios (star cluster inspiral and Hills mechanism). We focus on the most pressing challenges that must be faced to shed light on the process of star formation in the vicinity of a SMBH.Comment: 68 pages, 35 figures; invited review chapter, to be published in expanded form in Haardt, F., Gorini, V., Moschella, U. and Treves, A., 'Astrophysical Black Holes'. Lecture Notes in Physics. Springer 201