A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes

Peptides that are antigenic for T lymphocytes are ligands for two receptors, the class I or II glycoproteins that are encoded by genes in the major histocompatibility complex, and the idiotypic / chain T-cell antigen receptor1–9. That a peptide must bind to an MHC molecule to interact with a T-cell antigen receptor is the molecular basis of the MHC restriction of antigen-recognition by T lymphocytes10,11. In such a trimolecular interaction the amino-acid sequence of the peptide must specify the contact with both receptors: agretope residues bind to the MHC receptor and epitope residues bind to the T-cell antigen receptor12,13. From a compilation of known antigenic peptides, two algorithms have been proposed to predict antigenic sites in proteins. One algorithm uses linear motifs in the sequence14, whereas the other considers peptide conformation and predicts antigenicity for amphipathic -helices15,16. We report here that a systematic delimitation of an antigenic site precisely identifies a predicted pentapeptide motif as the minimal antigenic determinant presented by a class I MHC molecule and recognized by a cytolytic T lymphocyte clone

Multi-Magnon Scattering in the Ferromagnetic XXX-Model with Inhomogeneities

We determine the transition amplitude for multi-magnon scattering induced through an inhomogeneous distribution of the coupling constant in the ferromagnetic XXX-model. The two and three particle amplitudes are explicitely calculated at small momenta. This suggests a rather plausible conjecture also for a formula of the general n-particle amplitude.Comment: 21 pages, latex, no figure

Diagonalization of an Integrable Discretization of the Repulsive Delta Bose Gas on the Circle

We introduce an integrable lattice discretization of the quantum system of n bosonic particles on a ring interacting pairwise via repulsive delta potentials. The corresponding (finite-dimensional) spectral problem of the integrable lattice model is solved by means of the Bethe Ansatz method. The resulting eigenfunctions turn out to be given by specializations of the Hall-Littlewood polynomials. In the continuum limit the solution of the repulsive delta Bose gas due to Lieb and Liniger is recovered, including the orthogonality of the Bethe wave functions first proved by Dorlas (extending previous work of C.N. Yang and C.P. Yang).Comment: 25 pages, LaTe

A Conditional Yeast E1 Mutant Blocks the Ubiquitin–Proteasome Pathway and Reveals a Role for Ubiquitin Conjugates in Targeting Rad23 to the Proteasome

E1 ubiquitin activating enzyme catalyzes the initial step in all ubiquitin-dependent processes. We report the isolation of uba1-204, a temperature-sensitive allele of the essential Saccharomyces cerevisiae E1 gene, UBA1. Uba1-204 cells exhibit dramatic inhibition of the ubiquitin–proteasome system, resulting in rapid depletion of cellular ubiquitin conjugates and stabilization of multiple substrates. We have employed the tight phenotype of this mutant to investigate the role ubiquitin conjugates play in the dynamic interaction of the UbL/UBA adaptor proteins Rad23 and Dsk2 with the proteasome. Although proteasomes purified from mutant cells are intact and proteolytically active, they are depleted of ubiquitin conjugates, Rad23, and Dsk2. Binding of Rad23 to these proteasomes in vitro is enhanced by addition of either free or substrate-linked ubiquitin chains. Moreover, association of Rad23 with proteasomes in mutant and wild-type cells is improved upon stabilizing ubiquitin conjugates with proteasome inhibitor. We propose that recognition of polyubiquitin chains by Rad23 promotes its shuttling to the proteasome in vivo

InterPro in 2017-beyond protein family and domain annotations

InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences

Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods

The promiscuous activity of the enzyme o-succinylbenzoate synthase (OSBS) from the actinobacteria Amycolatopsis is investigated by means of QM/MM methods, using both density functional theory and semiempirical Hamiltonians. This enzyme catalyzes not only the dehydration of 2-succinyl-6R-hydroxy-2,4-cyclohexadiene-1R-carboxylate but also catalyzes racemization of different acylamino acids, with N-succinyl-R-phenylglycine being the best substrate. We investigated the molecular mechanisms for both reactions exploring the potential energy surface. Then, molecular dynamics simulations were performed to obtain the free energy profiles and the averaged interaction energies of enzymatic residues with the reacting system. Our results confirm the plausibility of the reaction mechanisms proposed in the literature, with a good agreement between theoretical and experimentally derived activation free energies. Our simulations unravel the role played by the different residues in each of the two possible reactions. The presence of flexible loops in the active site and the selection of structural modifications in the substrate seem to be key elements to promote the promiscuity of this enzyme.This work was supported by the Spanish Ministerio de Economia y Competitividad project CTQ2012-36253-C03-03 ́ and FEDER funds. K.S. thanks the Polish National Science Center (NCN) for Grant 2011/02/A/ST4/00246. The authors acknowledge computational facilities of the Servei d’Informatica ̀ de la Universitat de Valencia in the ̀ “Tirant” supercomputer, which is part of the Spanish Supercomputing Network

System engineering toolbox for design-oriented engineers

This system engineering toolbox is designed to provide tools and methodologies to the design-oriented systems engineer. A tool is defined as a set of procedures to accomplish a specific function. A methodology is defined as a collection of tools, rules, and postulates to accomplish a purpose. For each concept addressed in the toolbox, the following information is provided: (1) description, (2) application, (3) procedures, (4) examples, if practical, (5) advantages, (6) limitations, and (7) bibliography and/or references. The scope of the document includes concept development tools, system safety and reliability tools, design-related analytical tools, graphical data interpretation tools, a brief description of common statistical tools and methodologies, so-called total quality management tools, and trend analysis tools. Both relationship to project phase and primary functional usage of the tools are also delineated. The toolbox also includes a case study for illustrative purposes. Fifty-five tools are delineated in the text

Satellite‐Based Monitoring of Irrigation Water Use: Assessing Measurement Errors and Their Implications for Agricultural Water Management Policy

Reliable accounting of agricultural water use is critical for sustainable water management. However, the majority of agricultural water use is not monitored, with limited metering of irrigation despite increasing pressure on both groundwater and surface water resources in many agricultural regions worldwide. Satellite remote sensing has been proposed as a low-cost and scalable solution to fill widespread gaps in monitoring of irrigation water use in both developed and developing countries, bypassing the technical, socioeconomic, and political challenges that to date have constrained in situ metering. In this paper, we show through a systematic meta-analysis that the relative accuracy of different satellite-based irrigation water use monitoring approaches remains poorly understood, with evidence of large uncertainties when water use estimates are validated against in situ irrigation data at both field and regional scales. Subsequently, we demonstrate that water use measurement errors result in large economic welfare losses for farmers and may negatively impact ability of policies to limit acute and nonlinear externalities of irrigation abstraction on both the environment and other water users. Our findings highlight that water resource planners must consider the trade-offs between accuracy and costs associated with different water use accounting approaches. Remote sensing has an important role to play in supporting improved agricultural water accounting—both independently and in combination with in situ monitoring. However, greater transparency and evidence is needed about underlying uncertainties in satellite-based models, along with how these measurement errors affect the performance of associated policies to manage different short- and long-term externalities of irrigation water use