Engineering amyloidogenicity towards the development of nanofibrillar materials

When folded into their native structures, proteins in biological systems function as nanostructured machines. By contrast, some polypeptides tend to aggregate into other well-ordered structures, namely amyloid fibrils. Such well-ordered protein fibrils are attractive materials for nanobiotechnology because they self-associate through noncovalent bonds under controlled conditions - a property that is shared with small organic molecules called organogelators. Recently, the use of amyloid fibrils as structural templates for constructing nanowires has been demonstrated. Such applications will potentially become one of the next trends in protein engineering and nanobiotechnology.     

Advances in Nano Biotic/Abiotic Hybrid Systems: Protein-Based Engineered Devices

Integrative nanobiotechnology utilizes natural ideas and materials for manufacturing nanoscale devices. As living organisms traditionally represent a good model for engineers to learn from, biological components of interest, with optimal functionality, have been used in the creation of biotic/abiotic hybrid devices. As an example, bacteriorhodopsin/F₀F₁-ATP-synthase-incorporated polymer vesicles provide a model of hybrid protein/artificial synthetic membrane system to perform biological functions. Some potential applications are the construction of intervesicular/intravesicular communications, such as excitable vesicles (EVs), for biocomputer and biomolecular motor-powered nanoelectromechanical systems (NEMS) for nanomedicine. Finally, advanced biotic/abiotic hybrid technology is expected to provide an alternative method to conventional fabrication technology to meet the increasing demands by saving enormous engineering efforts.     

Semi-synthetic nucleic acid-protein conjugates: applications in life sciences and nanobiotechnology

Semi-synthetic conjugates of nucleic acids and proteins can be generated by either covalent coupling chemistry, or else by non-covalent biomolecular recognition systems, such as receptor-ligands of complementary nucleic acids. These nucleic acid-protein conjugates are versatile molecular tools which can be applied, for instance, in the self-assembly of high-affinity reagents for immunological detection assays, the fabrication of laterally microstructured biochips containing functional biological groups, and the biomimetic 'bottom-up' synthesis of nanostructured supramolecular devices. This review summarizes the current state-of-the-art synthesis and characterization methods of artificial nucleic acid-protein conjugates, as well as applications and perspectives for future developments of such hybrid biomolecular components in life sciences and nanobiotechnology.     

Manipulating redox systems: application to nanotechnology

Redox proteins and enzymes are attractive targets for nanobiotechnology. The theoretical framework of biological electron transfer is increasingly well-understood, and several properties make redox centres good systems for exploitation: many can be detected both electrochemically and optically; they can perform specific reactions; they are capable of self-assembly; and their dimensions are in the nanoscale. Great progress has been made with the two main approaches of protein engineering: rational design and combinatorial synthesis. Rational design has put our understanding of the structure-function relationship to the test, whereas combinatorial synthesis has generated new molecules of interest. This article provides selected examples of novel approaches where redox proteins are "wired up" in efficient electron-transfer chains, are "assembled" in artificial multidomain structures (molecular Lego), are "linked" to surfaces in nanodevices for biosensing and nanobiotechnological applications.     

DNA Binding and Bending Protein-Based DNA Actuator and its Practical Realization

In the life forms, the biomolecules such as DNA and protein are interacting with each other to maintain their life activity. Simultaneously, these biomolecules form DNA–protein complexes; as a result, the life forms can adjust to the external environment and continue its life activities. Therefore, using these characteristics of the DNA recognition ability of proteins, the novel molecular devices can be established. Here, we show the application of DNA binding and bending protein for design of the DNA actuator and its practical realization. The single polypeptide chain integrated host factor 2 (scIHF2), which is a DNA binding and bending protein, was used to bind to and/or bend the specific domains of DNA. Using this protein and designing the sequences of DNA, mechanical-functionalized DNA-based biomolecular device could be fabricated. Using these mechanisms, DNA binding and bending proteins have great potentials for establishing the DNA actuator for nanobiotechnology and nanotechnology applications.     

Emerging Applications of Bacterial Spores in Nanobiotechnology

Bacterial spores are robust and dormant life forms with formidable resistance properties, in part, attributable to the multiple layers of protein that encase the spore in a protective and flexible shield. The coat has a number of features pertinent to the emerging field of nanobiotechnology including self-assembling protomers and the capacity for engineering and delivery of foreign molecules. This review gives an account of recent progress describing the use of the spore, and specifically, the spore coat as a vehicle for heterologous antigen presentation and protective immunization (vaccination). As interest in the spore coat increases it seems likely that they will be exploited further for drug and enzyme delivery as well as a source of novel self-assembling proteins.     

Nanoinformatics: an emerging area of information technology at the intersection of bioinformatics, computational chemistry and nanobiotechnology

After the progress made during the genomics era, bioinformatics was tasked with supporting the flow of information generated by nanobiotechnology efforts. This challenge requires adapting classical bioinformatic and computational chemistry tools to store, standardize, analyze, and visualize nanobiotechnological information. Thus, old and new bioinformatic and computational chemistry tools have been merged into a new sub-discipline: nanoinformatics. This review takes a second look at the development of this new and exciting area as seen from the perspective of the evolution of nanobiotechnology applied to the life sciences. The knowledge obtained at the nano-scale level implies answers to new questions and the development of new concepts in different fields. The rapid convergence of technologies around nanobiotechnologies has spun off collaborative networks and web platforms created for sharing and discussing the knowledge generated in nanobiotechnology. The implementation of new database schemes suitable for storage, processing and integrating physical, chemical, and biological properties of nanoparticles will be a key element in achieving the promises in this convergent field. In this work, we will review some applications of nanobiotechnology to life sciences in generating new requirements for diverse scientific fields, such as bioinformatics and computational chemistry.     

Pup-蛋白酶体系统的作用机制和生物学功能

Pup-蛋白酶体系统（Pup-proteasome system,PPS）是原核生物的一种翻译后蛋白质修饰降解体系,在去酰胺酶（deamidase of Pup,Dop）和蛋白酶体辅助因子A (proteasome accessory factorA,PafA)两种酶的作用下,原核生物类泛素蛋白（prokaryotic ubiquitin-like protein,Pup）可以标记靶蛋白,并介导靶蛋白经蛋白酶体降解。在分枝杆菌中PPS参与氧化应激、营养缺乏、热激、DNA损伤等多种应激反应,并在金属离子稳态调控、毒素-抗毒素系统（toxin-antitoxin system,TA system）的调节以及抵抗宿主免疫等过程中发挥作用。PPS与结核分枝杆菌（Mycobacterium tuberculosis,Mtb）的持留性和致病性直接相关,因此PPS中的PafA、Dop和蛋白酶体均是抗结核药物开发的新靶点,筛选针对PPS的小分子抑制剂将成为新型抗结核药物研发的一个新途径。此外,Paf A催化的蛋白质Pup化被应用于生物技术的研发,形成了一种新的邻近标记技术——基于Pup化的邻近标记技术...     

Rationally engineering natural protein assemblies in nanobiotechnology

Multimeric protein assemblies are essential components in viruses, bacteria, eukaryotic cells, and organisms where they act as cytoskeletal scaffold, storage containers, or for directional transport. The bottom-up structures can be exploited in nanobiotechnology by harnessing their built-in properties and combining them with new functional modules. This review summarizes the design principles of natural protein assemblies, highlights recent progress in their structural elucidation, and shows how rational engineering can create new biomaterials for applications in vaccine development, biocatalysis, materials science, and synthetic biology.     

Opportunities in the design and application of RNA for gene expression control

The past decade of synthetic biology research has witnessed numerous advances in the development of tools and frameworks for the design and characterization of biological systems. Researchers have focused on the use of RNA for gene expression control due to its versatility in sensing molecular ligands and the relative ease by which RNA can be modeled and designed compared to proteins. We review the recent progress in the field with respect to RNA-based genetic devices that are controlled through small molecule and protein interactions. We discuss new approaches for generating and characterizing these devices and their underlying components. We also highlight immediate challenges, future directions and recent applications of synthetic RNA devices in engineered biological systems.     

The selection of aptamers specific for membrane molecular targets

A growing number of RNA aptamers have been selected experimentally using the SELEX combinatorial approach, and these aptamers have several advantages over monoclonal protein antibodies or peptides with respect to their applications in medicine and nanobiotechnology. Relatively few successful selections have been reported for membrane molecular targets, in contrast to the situation with non-membrane molecular targets. This review compares the procedures and techniques used in selections against membrane proteins and membrane lipids. In the case of membrane proteins, the selections were performed against soluble protein fragments, detergent-membrane protein mixed micelles, whole cells, vesicles derived from cellular membranes, and enveloped viruses. Liposomes were used as an experimental system for the selection of aptamers against membrane lipids. RNA structure-dependent aptamer binding for rafts in lipid vesicles was reported. Based on the selected aptamers against DOPC and the amino acid tryptophan, a specific passive membrane transporter composed of RNA was constructed. The determination of the selectivity of aptamers appears to be a crucial step in a selection, but has rarely been fully investigated. The selections, which use whole cells or vesicles derived from membranes, can yield aptamers not only against proteins but also against membrane lipids.     

Protein kinases in elicitor signal transduction in plant cells

Plants have the ability to respond to pathogen invasion by specific defense reactions. Components of mammalian signal transduction chains have been identified in plants, and several lines of evidence have implicated such components in elicitor signal transmission in defense responses. In particular, it has been assumed that elicitor signals are transduced via a protein kinase cascade, although the identity of the protein kinases and the function of the phosphorylated proteins remain to be determined. The purpose of this review is to discuss the roles of protein kinases in elicitor signal transduction pathways in plant cells based on recent progress in this field.     

纳米生物技术

纳米生物技术将纳米技术和生物技术有机集成 ,将成为现代生物工程的重要组成部分 ,简要介绍纳米生物技术中的纳米生物材料 ,生物芯片、分子马达、纳米探针等方面的最新进展。     

Protein structure comparison: implications for the nature of 'fold space', and structure and function prediction

The identification of geometric relationships between protein structures offers a powerful approach to predicting the structure and function of proteins. Methods to detect such relationships range from human pattern recognition to a variety of mathematical algorithms. A number of schemes for the classification of protein structure have found widespread use and these implicitly assume the organization of protein structure space into discrete categories. Recently, an alternative view has emerged in which protein fold space is seen as continuous and multidimensional. Significant relationships have been observed between proteins that belong to what have been termed different 'folds'. There has been progress in the use of these relationships in the prediction of protein structure and function.     

Molecular Simulations of Gram-Negative Bacterial Membranes: A Vignette of Some Recent Successes

In the following review we use recent examples from the literature to discuss progress in the area of atomistic and coarse-grained molecular dynamics simulations of selected bacterial membranes and proteins, with a particular focus on Gram-negative bacteria. As structural biology continues to provide increasingly high-resolution data on the proteins that reside within these membranes, simulations have an important role to play in linking these data with the dynamical behavior and function of these proteins. In particular, in the last few years there has been significant progress in addressing the issue of biochemical complexity of bacterial membranes such that the heterogeneity of the lipid and protein components of these membranes are now being incorporated into molecular-level models. Thus, in future we can look forward to complementary data from structural biology and molecular simulations combining to provide key details of structure-dynamics-function relationships in bacterial membranes.     

Well-defined protein–polymer conjugates—synthesis and potential applications

During the last decades, numerous studies have focused on combining the unique catalytic/functional properties and structural characteristics of proteins and enzymes with those of synthetic molecules and macromolecules. The aim of such multidisciplinary studies is to improve the properties of the natural component, combine them with those of the synthetic, and create novel biomaterials in the nanometer scale. The specific coupling of polymers onto the protein structures has proved to be one of the most straightforward and applicable approaches in that sense. In this article, we focus on the synthetic pathways that have or can be utilized to specifically couple proteins to polymers. The different categories of well-defined protein–polymer conjugates and the effect of the polymer on the protein function are discussed. Studies have shown that the specific conjugation of a synthetic polymer to a protein conveys its physico-chemical properties and, therefore, modifies the biodistribution and solubility of the protein, making it in certain cases soluble and active in organic solvents. An overview of the applications derived from such bioconjugates in the pharmaceutical industry, biocatalysis, and supramolecular nanobiotechnology is presented at the final part of the article.     

Engineering tubulin: microtubule functionalization approaches for nanoscale device applications

With the emergences of engineered devices at microscale and nanoscale dimensions, there is a growing need for controlled actuation and transport at these length scales. The kinesin–microtubule system provides a highly evolved biological transport system well suited for these tasks. Accordingly, there is an ongoing effort to create hybrid nanodevices that integrate biological components with engineered materials for applications such as biological separations, nanoscale assembly, and sensing. Adopting microtubules for these applications generally requires covalent attachment of biotin, fluorophores, or other biomolecules to tubulin enable surface or cargo attachment, or visualization. This review summarizes different strategies for functionalizing microtubules for application-focused as well as basic biological research. These functionalization strategies must maintain the integrity of microtubule proteins so that they do not depolymerize and can be transported by kinesin motors, while adding utility such as the ability to reversibly bind cargo. The relevant biochemical and electrical properties of microtubules are discussed, as well as strategies for microtubule stabilization and long-term storage. Next, attachment strategies, such as antibodies and DNA hybridization that have proven useful to date, are discussed in the context of ongoing hybrid nanodevice research. The review concludes with a discussion of less explored opportunities, such as harnessing the utility of tubulin posttranslational modifications and the use of recombinant tubulin that may enable future progress in nanodevice development.     

Trafficking regulation of proteins in Alzheimer’s disease

The β-amyloid (Aβ) peptide has been postulated to be a key determinant in the pathogenesis of Alzheimer’s disease (AD). Aβ is produced through sequential cleavage of the β-amyloid precursor protein (APP) by β- and γ-secretases. APP and relevant secretases are transmembrane proteins and traffic through the secretory pathway in a highly regulated fashion. Perturbation of their intracellular trafficking may affect dynamic interactions among these proteins, thus altering Aβ generation and accelerating disease pathogenesis. Herein, we review recent progress elucidating the regulation of intracellular trafficking of these essential protein components in AD.     

An ubiquitin ligase recognizing a protein oxidized by iron: implications for the turnover of oxidatively damaged proteins

Protein oxidation is a natural consequence of aerobic metabolism in cells. Oxidative modification of amino acid residues of proteins causes to lose activity or function of proteins. Organisms have thus developed pathways to remove oxidized proteins by rapid protein degradation. These pathways are important components in cellular quality control mechanisms. It has been suggested that oxidized proteins are degraded by the proteasome. However, whether ubiquitylation is necessary for the degradation of oxidized proteins remains a controversial issue. We have recently identified HOIL-1 (heme-oxidized IRP2 ubiquitin ligase-1) as an E3 ligase that recognizes a protein that has been oxidized by iron. This review describes the recent progress made in understanding the ubiquitin-proteolytic pathway and the regulation of iron metabolism. The process involved in eliminating oxidized proteins and the possible roles that HOIL-1 ubiquitin ligase may play in these processes are discussed.     

Peroxisome biogenesis

Peroxisomes are eukaryotic organelles that are the subcellular location of important metabolic reactions. In humans, defects in the organelle's function are often lethal. Yet, relative to other organelles, little is known about how cells maintain and propagate peroxisomes or how they direct specific sets of newly synthesized proteins to these organelles (peroxisome biogenesis/assembly). In recent years, substantial progress has been made in elucidating aspects of peroxisome biogenesis and in identifying PEX genes whose products, peroxins, are essential for one or more of these processes. The most progress has been made in understanding the mechanism by which peroxisome matrix proteins are imported into the organelles. Signal sequences responsible for targeting proteins to the organelle have been defined. Potential signal receptor proteins, a receptor docking protein and other components of the import machinery have been identified, along with insights into how they operate. These studies indicate that multiple peroxisomal protein-import mechanisms exist and that these mechanisms are novel, not simply variations of those described for other organelles.