Full-length structural model of RET3 and SEC21 in COPI: identification of binding sites on the appendage for accessory protein recruitment motifs

COPI, a 600 kD heptameric complex (consisting of subunits α, β, γ, δ, ε, ζ, and β′) “coatomer,” assembles non-clathrin-coated vesicles and is responsible for intra-Golgi and Golgi-to-ER protein trafficking. Here, we report the three-dimensional structures of the entire sequences of yeast Sec21 (γ-COPI mammalian ortholog), yeast Ret3 (ζ-COPI mammalian ortholog), and the results of successive molecular dynamics investigations of the subunits and assembly based on a protein–protein docking experiment. The three-dimensional structures of the subunits in their complexes indicate the residues of the two subunits that impact on assembly, the conformations of Ret3 and Sec21, and their binding orientations in the complexed state. The structure of the appendage domain of Sec21, with its two subdomains—the platform and the β-sandwich, was investigated to explore its capacity to bind to accessory protein recruitment motifs. Our study shows that a binding site on the platform is capable of binding the Eps15 DPF and epsin DPW2 peptides, whereas the second site on the platform and the site on the β-sandwich subdomain were found to selectively bind to the amphiphysin FXDXF and epsin DPW1 peptides, respectively. Identifying the regions of both the platform and sandwich subdomains involved in binding each peptide motif clarifies the mechanism through which the appendage domain of Sec21 engages with the accessory proteins during the trafficking process of non-clathrin-coated vesicles

Aerospace Medicine and Biology: A continuing bibliography with indexes (supplement 156)

This bibliography lists 170 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1976

Analyses of vesicular transport within the endoplasmic reticulum-golgi interface in "Saccharomyces cerevisiae"

A characteristic feature of every eukaryotic cell is its division into different compartments. This subdivision into different intracellular organelles like the endoplasmic reticulum (ER), the Golgi apparatus or the endosomal/lysosomal system enables cells to provide the appropriate environment for a great variety of biochemical processes. However, it also necessitates an elaborate machinery for the communication between these compartments or organelles. On one hand, material has to be exchanged between organelles, but on the other hand, their integrity with respect to their protein and lipid content, has to be maintained to fulfil their function. Transport processes between different organelles are mediate by intracellular traffic pathways. Proteins enter the secretory pathway at the ER, where they acquire first posttranslational modifications. From the ER, they are delivered to the Golgi, where they are further modified and sorted to their target compartments. In the secretory pathway, transport carriers, so-called vesicles, bud from one organelle (donor) and fuse with the next organelle (acceptor) along their trafficking route. Understanding the molecular mechanisms and regulations underlying vesicular transport is crucial and therefore has been a main topic of research over the last decades. The machinery required for budding and fusion of vesicles along their trafficking pathways is conserved from yeast to human. Therefore, the yeast Saccharomyces cerevisiae represents a suitable organism to study the secretory pathway. In this thesis, we used S. cerevisiae to examine the regulation of vesicular traffic at the ER-Golgi interface, more specifically the fusion of vesicles with ER membranes. The consumption of a vesicle at its target membrane is mediated by the orchestrated action of various members of conserved protein families that act in a regulated manner. Main players involved in vesicular fusion are Rab GTPases, tethering factors and SNAREs. The tethering factors and the Rab GTPases mediate the first contact of an incoming vesicle with its acceptor organelle, whereas the SNARE proteins are responsible for the final fusion event between vesicles and target membranes. Here, we identified the Rab GTPase Ypt1p as mediator of vesicle fusion with the ER. Moreover, Ypt1p was not only required for vesicle fusion at the ER, but also for the maintenance of the morphology and protein composition of the Golgi, and for vesicle formation at the Golgi. In addition, the tethering complex responsible for the docking of Golgi-derived vesicles with the ER, the Dsl1 tethering complex was analyzed. We found that this complex, apart from mediating the first contact of the incoming vesicles with the ER membrane, seems to play an additional role in proofreading and stabilization of SNARE complexes that are responsible for vesicle fusion at the E

Animal thermoregulation: a review of insulation, physiology and behaviour relevant to temperature control in buildings

Birds and mammals have evolved many thermal adaptations that are relevant to the bioinspired design of temperature control systems and energy management in buildings. Similar to many buildings, endothermic animals generate internal metabolic heat, are well insulated, regulate their temperature within set limits, modify microclimate and adjust thermal exchange with their environment. We review the major components of animal thermoregulation in endothermic birds and mammals that are pertinent to building engineering, in a world where climate is changing and reduction in energy use is needed. In animals, adjustment of insulation together with physiological and behavioural responses to changing environmental conditions fine-tune spatial and temporal regulation of body temperature, while also minimizing energy expenditure. These biological adaptations are characteristically flexible, allowing animals to alter their body temperatures to hourly, daily, or annual demands for energy. They exemplify how buildings could become more thermally reactive to meteorological fluctuations, capitalising on dynamic thermal materials and system properties. Based on this synthesis, we suggest that heat transfer modelling could be used to simulate these flexible biomimetic features and assess their success in reducing energy costs while maintaining thermal comfort for given building types

The Nuclear Pore Complex as a Flexible and Dynamic Gate

Nuclear pore complexes (NPCs) perforate the nuclear envelope and serve as the primary transport gates for molecular exchange between nucleus and cytoplasm. Stripping the megadalton complex down to its most essential organizational elements, one can divide the NPC into scaffold components and the disordered elements attached to them that generate a selective barrier between compartments. These structural elements exhibit flexibility, which may hold a clue in understanding NPC assembly and function. Here we review the current status of NPC research with a focus on the functional implications of its structural and compositional heterogeneity.National Institutes of Health (U.S.) (Grant R01GM077537)National Institutes of Health (U.S.) (Grant R01AR065484

Affective neuroscience, emotional regulation, and international relations

International relations (IR) has witnessed an emerging interest in neuroscience, particularly for its relevance to a now widespread scholarship on emotions. Contributing to this scholarship, this article draws on the subfields of affective neuroscience and neuropsychology, which remain largely unexplored in IR. Firstly, the article draws on affective neuroscience in illuminating affect's defining role in consciousness and omnipresence in social behavior, challenging the continuing elision of emotions in mainstream approaches. Secondly, it applies theories of depth neuropsychology, which suggest a neural predisposition originating in the brain's higher cortical regions to attenuate emotional arousal and limit affective consciousness. This predisposition works to preserve individuals' self-coherence, countering implicit assumptions about rationality and motivation within IR theory. Thirdly, it outlines three key implications for IR theory. It argues that affective neuroscience and neuropsychology offer a route towards deep theorizing of ontologies and motivations. It also leads to a reassessment of the social regulation of emotions, particularly as observed in institutions, including the state. It also suggests a productive engagement with constructivist and poststructuralist approaches by addressing the agency of the body in social relations. The article concludes by sketching the potential for a therapeutically-attuned approach to IR

Computational studies of biomembrane systems: Theoretical considerations, simulation models, and applications

This chapter summarizes several approaches combining theory, simulation and experiment that aim for a better understanding of phenomena in lipid bilayers and membrane protein systems, covering topics such as lipid rafts, membrane mediated interactions, attraction between transmembrane proteins, and aggregation in biomembranes leading to large superstructures such as the light harvesting complex of green plants. After a general overview of theoretical considerations and continuum theory of lipid membranes we introduce different options for simulations of biomembrane systems, addressing questions such as: What can be learned from generic models? When is it expedient to go beyond them? And what are the merits and challenges for systematic coarse graining and quasi-atomistic coarse grained models that ensure a certain chemical specificity

Design principles of hair-like structures as biological machines

Hair-like structures are prevalent throughout biology and frequently act to sense or alter interactions with an organism's environment. The overall shape of a hair is simple: a long, filamentous object that protrudes from the surface of an organism. This basic design, however, can confer a wide range of functions, owing largely to the flexibility and large surface area that it usually possesses. From this simple structural basis, small changes in geometry, such as diameter, curvature and inter-hair spacing, can have considerable effects on mechanical properties, allowing functions such as mechanosensing, attachment, movement and protection. Here, we explore how passive features of hair-like structures, both individually and within arrays, enable diverse functions across biology. Understanding the relationships between form and function can provide biologists with an appreciation for the constraints and possibilities on hair-like structures. Additionally, such structures have already been used in biomimetic engineering with applications in sensing, water capture and adhesion. By examining hairs as a functional mechanical unit, geometry and arrangement can be rationally designed to generate new engineering devices and ideas

Amphiphilic Macromolecules on Cell Membranes: From Protective Layers to Controlled Permeabilization.

International audienceAntimicrobial and cell-penetrating peptides have inspired developments of abiotic membrane-active polymers that can coat, penetrate, or break lipid bilayers in model systems. Application to cell cultures is more recent, but remarkable bioactivities are already reported. Synthetic polymer chains were tailored to achieve (i) high biocide efficiencies, and selectivity for bacteria (Gram-positive/Gram-negative or bacterial/mammalian membranes), (ii) stable and mild encapsulation of viable isolated cells to escape immune systems, (iii) pH-, temperature-, or light-triggered interaction with cells. This review illustrates these recent achievements highlighting the use of abiotic polymers, and compares the major structural determinants that control efficiency of polymers and peptides. Charge density, sp. of cationic and guanidinium side groups, and hydrophobicity (including polarity of stimuli-responsive moieties) guide the design of new copolymers for the handling of cell membranes. While polycationic chains are generally used as biocidal or hemolytic agents, anionic amphiphilic polymers, including Amphipols, are particularly prone to mild permeabilization and/or intracell delivery