Recognition and fluorescence sensing of specific amino acid residue on protein surface using designed molecules

Many biological processes are mediated by surface recognition between proteins. Small molecules that recognize and bind a specific region of a protein surface may be promising agents for disrupting certain protein-protein surface interactions, which consequently leads to regulation of cellar functions. This article describes our recent efforts toward the development of the designed small molecules, which can recognize histidine or phosphorylated amino acid residues on peptide surfaces in a sequence-selective manner. These results demonstrate that cooperative metal-ligand interaction is powerful for tight and selective binding to the specific amino acid residues of proteins in aqueous medium.     

PDZ结构域的结构特点及其识别特异性配体的机制

PDZ结构域作为介导蛋白质之间相互作用的重要结构域之一,参与到细胞内运输、离子通道、以及各种信号传导通路等多种生物学过程.PDZ结构域是由80~100个氨基酸组成的小的球状结构域,对某些多PDZ结构域蛋白来说,需要一前一后形成串联体才能正确折叠.另外,PDZ结构域相互之间也可以形成同源或异源二聚体.这些PDZ结构域的突出特点是能特异性地识别配体靶蛋白C末端短的氨基酸序列,但有些也能识别靶蛋白的内部β发夹结构.而一些支架蛋白的PDZ结构域与细胞膜上脂类的相互作用则增加了其与膜的亲和性.本文简要概括了PDZ结构域的结构特点及其对配体的各种特异性识别的机制,从而为研究各种PDZ蛋白的功能提供了结构基础.     

Individual recognition in ant queens

Personal relationships are the cornerstone of vertebrate societies, but insect societies are either too large for individual recognition, or their members were assumed to lack the necessary cognitive abilities . This paradigm has been challenged by the recent discovery that paper wasps recognize each other's unique facial color patterns . Individual recognition is advantageous when dominance hierarchies control the partitioning of work and reproduction . Here, we show that unrelated founding queens of the ant Pachycondyla villosa use chemical cues to recognize each other individually. Aggression was significantly lower in pairs of queens that had previously interacted than in pairs with similar social history but no experience with one another. Moreover, subordinates discriminated familiar and unfamiliar dominants in choice experiments in which physical contact, but not odor perception, was prevented and in tests with anaesthetized queens. The cuticular chemical profiles of queens were neither associated with dominance nor fertility and, therefore, do not represent status badges , and nestmate queens did not share a common odor. Personal recognition facilitates the maintenance of stable dominance hierarchies in these small societies. This suggests that the ability to discriminate between individual traits is selected for when it incurs net benefits for the resolution of conflict.     

Multimodal individual recognition in the crayfish cherax destructor

There is some evidence that macrurans recognize each other as individuals. In freshwater crayfish there are conflicting reports and there is limited information about the sensory mechanisms involved. To determine the extent to which the crayfish Cherax destructor is capable of individual recognition, we performed experiments that familiarized animals with each other and then manipulated their recent success in dominance contests. Crayfish were more likely to win an encounter when paired against a familiar opponent than an unfamiliar one after the manipulation stage. In other experiments, animals were attracted to familiar conspecifics when only visual or chemical cues were present. This demonstrates that C. destructor is able to discriminate between a familiar and an unfamiliar opponent. The results highlight the complex nature of intraspecific communication in crayfish and suggest elements likely to be of importance in the social interactions of groups in the wild state.     

On the possibility of improving the efficiency of cancer recognition and eradication in vivo when concurrently using two different types of nanodevices

When using nanodevices in oncology, it is necessary to provide efficiency of the performance of these nanodevices simultaneously with their safety for an organism. These are conflicting objectives to some extent. Nevertheless, as shown in this work, an approach that helps to eliminate this contradiction is offered. For recognition and destruction of cancer cells in vivo it is suggested to use, instead of one type, simultaneously two types of specialized nanodevices interacting with each other introduced into an organism. Some of the nanodevices only recognize cancer cells, while other ones, that cannot recognize them, find cells being marked by nanodevices of the first type, and destroy them. This makes it possible to increase the reliability of the cancer cell recognition process on the one hand, and have the process of their destruction rather safe for an organism on the other hand.     

Diversity of type II restriction endonucleases that require two DNA recognition sites

Orthodox Type IIP restriction endonucleases, which are commonly used in molecular biological work, recognize a single palindromic DNA recognition sequence and cleave within or near this sequence. Several new studies have reported on structural and biochemical peculiarities of restriction endonucleases that differ from the orthodox in that they require two copies of a particular DNA recognition sequence to cleave the DNA. These two sites requiring restriction endonucleases belong to different subtypes of Type II restriction endonucleases, namely Types IIE, IIF and IIS. We compare enzymes of these three types with regard to their DNA recognition and cleavage properties. The simultaneous recognition of two identical DNA sites by these restriction endonucleases ensures that single unmethylated recognition sites do not lead to chromosomal DNA cleavage, and might reflect evolutionary connections to other DNA processing proteins that specifically function with two sites.     

Recognition and molecular evolution in bacteria

One principal function of biological molecules in bacteria is to recognize other molecules. This allows cells to assemble for regulated enzymatic catalysis and the integration of biochemical pathways. Recognition is also an essential and a specific property in base pairing of DNA in the double helix. Therefore, recognition events must have been central to early self-assembly of primitive genetic material, genomes, cells, genetic recombination and especially in enzyme-substrate-product recognition events. Molecular recognition events are examined with an emphasis on their central role in early prokaryotic evolution.     

Structural compatibility of hydration shells as a criterion of mutual recognition of reacting biomolecules

Before a biochemical reaction begins to occur reagents need to recognize each other. To explain the recognition mechanism the «key-lock» hypothesis has been proposed at the end of the nineteenth century. Now it should be reconsidered since in the overwhelming majority of cases surface landscapes of the interacting molecules — individually and in the complex — do not coincide. The subsequent modifications of this hypothesis, for instance. the ligand-induced adjustment, were unable to predict a degree of the partner affinity and alleviate decision-making in essential task as to the search for the new drug forms. Here we offer a concept according to which the approaching reagents recognize each other by their hydration shells. Such an approach is based on the existence of universal structural blocks in water skeleton of biomolecules. The mutual recognition occurs when hydration shells of reagents are structurally compatible. This statement is demonstrated by the example of the simplest biochemical reaction.     

Why is the biological hydrophobicity scale more accurate than earlier experimental hydrophobicity scales?

The recognition of transmembrane helices by the translocon is primarily guided by the average hydrophobicity of the potential transmembrane helix. However, the exact hydrophobicity of each amino acid can be identified in several different ways. The free energy of transfer for amino acid analogues between a hydrophobic media, for example, octanol and water can be measured or obtained from simulations, the hydrophobicity can also be estimated by statistical properties from known transmembrane segments and finally the contribution of each amino acid type for the probability of translocon recognition has recently been measured directly. Although these scales correlate quite well, there are clear differences between them and it is not well understood which scale represents neither the biology best nor what the differences are. Here, we try to provide some answers to this by studying the ability of different scales to recognize transmembrane helices and predict the topology of transmembrane proteins. From this analysis it is clear that the biological hydrophobicity scale as well scales created from statistical analysis of membrane helices perform better than earlier experimental scales that are mainly based on measurements of amino acid analogs and not directly on transmembrane helix recognition. Using these results we identified the properties of the scales that perform better than other scales. We find, for instance, that the better performing scales consider proline more hydrophilic. This shows that transmembrane recognition is not only governed by pure hydrophobicity but also by the helix preferences for amino acids, as proline is a strong helix breaker. Proteins 2014; 82:2190–2198. © 2014 Wiley Periodicals, Inc.     

Zwitterionic capsular polysaccharides: the new MHCII-dependent antigens

The immune system has evolved the ability for T cells to recognize nearly any biological polymer, including peptides, protein superantigens, and glycolipids through presentation by the major histocompatibility complex (MHC) proteins such as MHC class I (MHCI), MHC class II (MHCII), and CD1. A recent and unexpected addition to this list is the zwitterionic capsular polysaccharide (ZPS). These bacterial molecules utilize MHCII presentation to activate T cells via recognition by alphabeta T cell receptor (alphabetaTCR) proteins. In this review, we explore what is currently known about ZPS processing and presentation within antigen-presenting cells (APCs) and the immune response that follows.     

Cell-cell recognition

The earlier step of morphogenesis is the segregation of cell lines which are homogeneous cell populations each endowed with its own specific developmental program. In order for the program to unfold in each line cells must be endowed with specific surface properties whereby the cells belonging to the same line can recognize each other as such in addition to recognizing those belonging to other cell lines as different. Experiments supporting this view are described. The hypothesis is presented that the cell-cell recognition system is phylogenetically linked with the invention of sexuality.     

Degrees make all the difference: The multifunctionality of histone H4 lysine 20 methylation

Residue and degree-specific methylation of histone lysines along with other epigenetic modifications organizes chromatin into distinct domains and regulates almost every aspect of DNA metabolism. Identification of histone methyltransferases and demethylases, as well as proteins that recognize methylated lysines, has clarified the role of each methylation event in regulating different biological pathways. Methylation of histone H4 lysine 20 (H4K20me) plays critical roles in diverse cellular processes such as gene expression, cell cycle progression and DNA damage repair, with each of the three degrees of methylation (mono- di- and tri-methylation) making a unique contribution. Here we discuss recent studies of H4K20me that have greatly improved our understanding of the regulation and function of this fascinating histone modification.     

Cross-species fertilization: the hamster egg receptor,Juno, binds the human sperm ligand,Izumo1

Fertilization is the culminating event in sexual reproduction and requires the recognition and fusion of the haploid sperm and egg to form a new diploid organism. Specificity in these recognition events is one reason why sperm and eggs from different species are not normally compatible. One notable exception is the unusual ability of zona-free eggs from the Syrian golden hamster (Mesocricetus auratus) to recognize and fuse with human sperm, a phenomenon that has been exploited to assess sperm quality in assisted fertility treatments. Following our recent finding that the interaction between the sperm and egg recognition receptors Izumo1 and Juno is essential for fertilization, we now demonstrate concordance between the ability of Izumo1 and Juno from different species to interact, and the ability of their isolated gametes to cross-fertilize each other in vitro. In particular, we show that Juno from the golden hamster can directly interact with human Izumo1. These data suggest that the interaction between Izumo1 and Juno plays an important role in cross-species gamete recognition, and may inform the development of improved prognostic tests that do not require the use of animals to guide the most appropriate fertility treatment for infertile couples.     

A Conserved Three-nucleotide Core Motif Defines Musashi RNA Binding Specificity

Musashi (MSI) family proteins control cell proliferation and differentiation in many biological systems. They are overexpressed in tumors of several origins, and their expression level correlates with poor prognosis. MSI proteins control gene expression by binding RNA and regulating its translation. They contain two RNA recognition motif (RRM) domains, which recognize a defined sequence element. The relative contribution of each nucleotide to the binding affinity and specificity is unknown. We analyzed the binding specificity of three MSI family RRM domains using a quantitative fluorescence anisotropy assay. We found that the core element driving recognition is the sequence UAG. Nucleotides outside of this motif have a limited contribution to binding free energy. For mouse MSI1, recognition is determined by the first of the two RRM domains. The second RRM adds affinity but does not contribute to binding specificity. In contrast, the recognition element for Drosophila MSI is more extensive than the mouse homolog, suggesting functional divergence. The short nature of the binding determinant suggests that protein-RNA affinity alone is insufficient to drive target selection by MSI family proteins.     

A model of visual recognition and categorization.

To recognize a previously seen object, the visual system must overcome the variability in the object''s appearance caused by factors such as illumination and pose. Developments in computer vision suggest that it may be possible to counter the influence of these factors, by learning to interpolate between stored views of the target object, taken under representative combinations of viewing conditions. Daily life situations, however, typically require categorization, rather than recognition, of objects. Due to the open-ended character of both natural and artificial categories, categorization cannot rely on interpolation between stored examples. Nonetheless, knowledge of several representative members, or prototypes, of each of the categories of interest can still provide the necessary computational substrate for the categorization of new instances. The resulting representational scheme based on similarities to prototypes appears to be computationally viable, and is readily mapped onto the mechanisms of biological vision revealed by recent psychophysical and physiological studies.     

Inhibition of cellular differentiation by phospholipase C: II. Separation of fusion and recognition among myogenic cells

Myogenic cells cultured in concentrations of phospholipase C which inhibit fusion still recognize each other. Recognition is accompanied by withdrawal from the cell cycle. We conclude that recognition and fusion are two distinct and separable processes and that fusion is preceded by cessation of cell division.     

Recognizing biological motion and emotions from point-light displays in autism spectrum disorders

One of the main characteristics of Autism Spectrum Disorder (ASD) are problems with social interaction and communication. Here, we explored ASD-related alterations in 'reading' body language of other humans. Accuracy and reaction times were assessed from two observational tasks involving the recognition of 'biological motion' and 'emotions' from point-light displays (PLDs). Eye movements were recorded during the completion of the tests. Results indicated that typically developed-participants were more accurate than ASD-subjects in recognizing biological motion or emotions from PLDs. No accuracy differences were revealed on two control-tasks (involving the indication of color-changes in the moving point-lights). Group differences in reaction times existed on all tasks, but effect sizes were higher for the biological and emotion recognition tasks. Biological motion recognition abilities were related to a person's ability to recognize emotions from PLDs. However, ASD-related atypicalities in emotion recognition could not entirely be attributed to more basic deficits in biological motion recognition, suggesting an additional ASD-specific deficit in recognizing the emotional dimension of the point light displays. Eye movements were assessed during the completion of tasks and results indicated that ASD-participants generally produced more saccades and shorter fixation-durations compared to the control-group. However, especially for emotion recognition, these altered eye movements were associated with reductions in task-performance.     

Carotenoid-binding proteins; accessories to carotenoid function

Understanding of the widespread biological importance of carotenoids is increasing. Accompanying this is the developing recognition that the interaction of carotenoids with other molecules, such as proteins, is also essential. Here the significance of carotenoid-protein interactions with respect to biological function is reviewed for three well characterised carotenoprotein complexes; crustacyanin, the orange carotenoid protein and glutathione-S-transferase P1. In addition a preliminary report is made on the recent partial purification of an echinenone-binding protein extracted from a New Zealand sea urchin, Evechinus chloroticus.     

Bile acids in asymmetric synthesis and chiral discrimination

An overview on the use of bile acid‐based compounds able to catalyze transformations, control the stereochemical course of a given reaction, recognize and bind other molecules, is presented. The recent developments in inclusion discrimination of chiral and achiral guests and enantioselective recognition achieved by bile acid are described with suitable examples. Chirality 2010. © 2009 Wiley‐Liss, Inc.