36,826 research outputs found

    Dynamic control of selectivity in the ubiquitination pathway revealed by an ASP to GLU substitution in an intra-molecular salt-bridge network

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    Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an “open”, binding competent, and a “closed”, binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch and allowed us to identify its components, namely an aspartate/glutamate pair, a lysine acting as the central switch and a remote aspartate. Perturbations of single residues in this network, both inside and outside the interaction surface, are sufficient to switch the global E2 interaction selectivity as demonstrated experimentally. Taken together, our results indicate a new mechanism to control E2-E3 interaction selectivity at an atomic level, highlighting how minimal changes in amino acid side-chain affecting the dynamics of intramolecular salt-bridges can be crucial for protein-protein interactions. These findings indicate that the widely accepted sequence-structure-function paradigm should be extended to sequence-structure-dynamics-function relationship and open new possibilities for control and fine-tuning of protein interaction selectivity

    Grasping bulky objects with two anthropomorphic hands

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    © 2016 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other worksThis paper presents an algorithm to compute precision grasps for bulky objects using two anthropomorphic hands. We use objects modeled as point clouds obtained from a sensor camera or from a CAD model. We then process the point clouds dividing them into two set of slices where we look for sets of triplets of points. Each triplet must accomplish some physical conditions based on the structure of the hands. Then, the triplets of points from each set of slices are evaluated to find a combination that satisfies the force closure condition (FC). Once one valid couple of triplets have been found the inverse kinematics of the system is computed in order to know if the corresponding points are reachable by the hands, if so, motion planning and a collision check are performed to asses if the final grasp configuration of the system is suitable. The paper inclu des some application examples of the proposed approachAccepted versio

    Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding

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    The MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis. Here we determined the crystal structures of MAGE- A3 and MAGE-A4. Both proteins crystallized with a terminal peptide bound in a deep cleft between two tandem-arranged winged helix domains. MAGE-A3 (but not MAGE-A4), is pre- dominantly dimeric in solution. Comparison of MAGE-A3 and MAGE-A3 with a structure of an effector-bound MAGE-G1 suggests that a major conformational rearrangement is required for binding, and that this conformational plasticity may be targeted by allosteric binders

    Ground Robotic Hand Applications for the Space Program study (GRASP)

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    This document reports on a NASA-STDP effort to address research interests of the NASA Kennedy Space Center (KSC) through a study entitled, Ground Robotic-Hand Applications for the Space Program (GRASP). The primary objective of the GRASP study was to identify beneficial applications of specialized end-effectors and robotic hand devices for automating any ground operations which are performed at the Kennedy Space Center. Thus, operations for expendable vehicles, the Space Shuttle and its components, and all payloads were included in the study. Typical benefits of automating operations, or augmenting human operators performing physical tasks, include: reduced costs; enhanced safety and reliability; and reduced processing turnaround time

    Autonomous Mechanical Assembly on the Space Shuttle: An Overview

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    The space shuttle will be equipped with a pair of 50 ft. manipulators used to handle payloads and to perform mechanical assembly operations. Although current plans call for these manipulators to be operated by a human teleoperator. The possibility of using results from robotics and machine intelligence to automate this shuttle assembly system was investigated. The major components of an autonomous mechanical assembly system are examined, along with the technology base upon which they depend. The state of the art in advanced automation is also assessed

    Preliminary Implementation of the Next Generation Cannulation Simulator

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    © 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Extracorporeal Membrane Oxygenation (ECMO) is a highly complex/critical lifesaving procedure known to support patients with cardiac and respiratory issues. Patients on ECMO are monitored 24/7 by a team of highly trained ECMO team comprising nurses, physicians, respiratory therapists, and perfusionists promptly intervening to any potential emergency situation. Simulation-Based Training (SBT) allows clinicians to experience and practice realistic hands-on procedures and scenarios without any risk. In ECMO, cannulation is a critical procedure performed to externally reroute the blood flow so it can be re-oxygenated by the ECMO machine before being recirculated through the patient's body. In a close collaboration with Hamad Medical Corporation (HMC), this project aims to develop a cost effective, realistic, and user-friendly ECMO simulator focusing on the venous and arterial cannulation procedure, The main features of this simulator include cannulation emergencies caused by low pressure flow, excessive force, recirculation, or mispositioned wire/cannula. Therefore, the ECMO cannulation simulator will not only greatly contribute to the initial and ongoing local training of HMC ECMO clinicians but also contribute to improving patient care by lowering the risks associated with the cannulation process

    AoA-aware Probabilistic Indoor Location Fingerprinting using Channel State Information

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    With expeditious development of wireless communications, location fingerprinting (LF) has nurtured considerable indoor location based services (ILBSs) in the field of Internet of Things (IoT). For most pattern-matching based LF solutions, previous works either appeal to the simple received signal strength (RSS), which suffers from dramatic performance degradation due to sophisticated environmental dynamics, or rely on the fine-grained physical layer channel state information (CSI), whose intricate structure leads to an increased computational complexity. Meanwhile, the harsh indoor environment can also breed similar radio signatures among certain predefined reference points (RPs), which may be randomly distributed in the area of interest, thus mightily tampering the location mapping accuracy. To work out these dilemmas, during the offline site survey, we first adopt autoregressive (AR) modeling entropy of CSI amplitude as location fingerprint, which shares the structural simplicity of RSS while reserving the most location-specific statistical channel information. Moreover, an additional angle of arrival (AoA) fingerprint can be accurately retrieved from CSI phase through an enhanced subspace based algorithm, which serves to further eliminate the error-prone RP candidates. In the online phase, by exploiting both CSI amplitude and phase information, a novel bivariate kernel regression scheme is proposed to precisely infer the target's location. Results from extensive indoor experiments validate the superior localization performance of our proposed system over previous approaches

    Robotic Grasping: A Generic Neural Network Architecture

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