scholarly journals Computational characterization of moonlighting proteins

2014 ◽  
Vol 42 (6) ◽  
pp. 1780-1785 ◽  
Author(s):  
Ishita K. Khan ◽  
Daisuke Kihara

Moonlighting proteins perform multiple independent cellular functions within one polypeptide chain. Moonlighting proteins switch functions depending on various factors including the cell-type in which they are expressed, cellular location, oligomerization status and the binding of different ligands at different sites. Although an increasing number of moonlighting proteins have been experimentally identified in recent years, the quantity of known moonlighting proteins is insufficient to elucidate their overall landscape. Moreover, most moonlighting proteins have been identified as a serendipitous discovery. Hence, characterization of moonlighting proteins using bioinformatics approaches can have a significant impact on the overall understanding of protein function. In this work, we provide a short review of existing computational approaches for illuminating the functional diversity of moonlighting proteins.

2006 ◽  
Vol 291 (6) ◽  
pp. C1121-C1128 ◽  
Author(s):  
Toni Gabaldón

Understanding a complex biological system, such as the mitochondrion, requires the identification of the complete repertoire of proteins targeted to the organelle, the characterization of these, and finally, the elucidation of the functional and physical interactions that occur within the mitochondrion. In the last decade, significant developments have contributed to increase our understanding of the mitochondrion, and among these, computational research has played a significant role. Not only general bioinformatics tools have been applied in the context of the mitochondrion, but also some computational techniques have been specifically developed to address problems that arose from within the mitochondrial research field. In this review the contribution of bioinformatics to mitochondrial biology is addressed through a survey of current computational methods that can be applied to predict which proteins will be localized to the mitochondrion and to unravel their functional interactions.


2020 ◽  
Vol 21 (8) ◽  
pp. 741-747
Author(s):  
Liguang Zhang ◽  
Yanan Shen ◽  
Wenjing Lu ◽  
Lengqiu Guo ◽  
Min Xiang ◽  
...  

Background: Although the stability of proteins is of significance to maintain protein function for therapeutical applications, this remains a challenge. Herein, a general method of preserving protein stability and function was developed using gelatin films. Method: Enzymes immobilized onto films composed of gelatin and Ethylene Glycol (EG) were developed to study their ability to stabilize proteins. As a model functional protein, β-glucosidase was selected. The tensile properties, microstructure, and crystallization behavior of the gelatin films were assessed. Result: Our results indicated that film configurations can preserve the activity of β-glucosidase under rigorous conditions (75% relative humidity and 37°C for 47 days). In both control films and films containing 1.8 % β-glucosidase, tensile strength increased with increased EG content, whilst the elongation at break increased initially, then decreased over time. The presence of β-glucosidase had a negligible influence on tensile strength and elongation at break. Scanning electron-microscopy (SEM) revealed that with increasing EG content or decreasing enzyme concentrations, a denser microstructure was observed. Conclusion: In conclusion, the dry film is a promising candidate to maintain protein stabilization and handling. The configuration is convenient and cheap, and thus applicable to protein storage and transportation processes in the future.


2021 ◽  
Vol 22 (5) ◽  
pp. 2501
Author(s):  
Sonja Hinz ◽  
Dominik Jung ◽  
Dorota Hauert ◽  
Hagen S. Bachmann

Geranylgeranyltransferase type-I (GGTase-I) represents an important drug target since it contributes to the function of many proteins that are involved in tumor development and metastasis. This led to the development of GGTase-I inhibitors as anti-cancer drugs blocking the protein function and membrane association of e.g., Rap subfamilies that are involved in cell differentiation and cell growth. In the present study, we developed a new NanoBiT assay to monitor the interaction of human GGTase-I and its substrate Rap1B. Different Rap1B prenylation-deficient mutants (C181G, C181S, and ΔCQLL) were designed and investigated for their interaction with GGTase-I. While the Rap1B mutants C181G and C181S still exhibited interaction with human GGTase-I, mutant ΔCQLL, lacking the entire CAAX motif (defined by a cysteine residue, two aliphatic residues, and the C-terminal residue), showed reduced interaction. Moreover, a specific, peptidomimetic and competitive CAAX inhibitor was able to block the interaction of Rap1B with GGTase-I. Furthermore, activation of both Gαs-coupled human adenosine receptors, A2A (A2AAR) and A2B (A2BAR), increased the interaction between GGTase-I and Rap1B, probably representing a way to modulate prenylation and function of Rap1B. Thus, A2AAR and A2BAR antagonists might be promising candidates for therapeutic intervention for different types of cancer that overexpress Rap1B. Finally, the NanoBiT assay provides a tool to investigate the pharmacology of GGTase-I inhibitors.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins specifically located in the cytoplasm, and two more in secreted proteins. Our results support the hypothesis that the characterization of Avoided Motifs in particular contexts can provide us with information about functional motifs, pointing to a new approach in the use of molecular sequences for the discovery of protein function.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.


2013 ◽  
Vol 28 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Marica Gemei ◽  
Rosa Di Noto ◽  
Peppino Mirabelli ◽  
Luigi Del Vecchio

In colorectal cancer, CD133+ cells from fresh biopsies proved to be more tumorigenic than their CD133– counterparts. Nevertheless, the function of CD133 protein in tumorigenic cells seems only marginal. Moreover, CD133 expression alone is insufficient to isolate true cancer stem cells, since only 1 out of 262 CD133+ cells actually displays stem-cell capacity. Thus, new markers for colorectal cancer stem cells are needed. Here, we show the extensive characterization of CD133+ cells in 5 different colon carcinoma continuous cell lines (HT29, HCT116, Caco2, GEO and LS174T), each representing a different maturation level of colorectal cancer cells. Markers associated with stemness, tumorigenesis and metastatic potential were selected. We identified 6 molecules consistently present on CD133+ cells: CD9, CD29, CD49b, CD59, CD151, and CD326. By contrast, CD24, CD26, CD54, CD66c, CD81, CD90, CD99, CD112, CD164, CD166, and CD200 showed a discontinuous behavior, which led us to identify cell type-specific surface antigen mosaics. Finally, some antigens, e.g. CD227, indicated the possibility of classifying the CD133+ cells into 2 subsets likely exhibiting specific features. This study reports, for the first time, an extended characterization of the CD133+ cells in colon carcinoma cell lines and provides a “dictionary” of antigens to be used in colorectal cancer research.


Cell Calcium ◽  
2021 ◽  
Vol 94 ◽  
pp. 102334
Author(s):  
Xin Su ◽  
Tamara Vasilkovska ◽  
Nicole Fröhlich ◽  
Olga Garaschuk

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