scholarly journals Sequence and Structure-Based Analyses of Human Ankyrin Repeats

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 423
Author(s):  
Broto Chakrabarty ◽  
Nita Parekh
Keyword(s):  
Sequence Similarity ◽  
Ankyrin Repeat ◽  
Centrality Measures ◽  
Compositional Bias ◽  
Cell Cycle Regulators ◽  
Conserved Residues ◽  
Signal Transducers ◽  
Ankyrin Repeat Proteins ◽  
Ankyrin Protein ◽  
And Function

Ankyrin is one of the most abundant protein repeat families found across all forms of life. It is found in a variety of multi-domain and single domain proteins in humans with diverse number of repeating units. They are observed to occur in several functionally diverse proteins, such as transcriptional initiators, cell cycle regulators, cytoskeletal organizers, ion transporters, signal transducers, developmental regulators, and toxins, and, consequently, defects in ankyrin repeat proteins have been associated with a number of human diseases. In this study, we have classified the human ankyrin proteins into clusters based on the sequence similarity in their ankyrin repeat domains. We analyzed the amino acid compositional bias and consensus ankyrin motif sequence of the clusters to understand the diversity of the human ankyrin proteins. We carried out network-based structural analysis of human ankyrin proteins across different clusters and showed the association of conserved residues with topologically important residues identified by network centrality measures. The analysis of conserved and structurally important residues helps in understanding their role in structural stability and function of these proteins. In this paper, we also discuss the significance of these conserved residues in disease association across the human ankyrin protein clusters.

TBC proteins: GAPs for mammalian small GTPase Rab?

2011 ◽  
Vol 31 (3) ◽  
pp. 159-168 ◽  
Author(s):  
Mitsunori Fukuda
Keyword(s):  
Insulin Resistance ◽  
Small Gtpases ◽  
Structure And Function ◽  
Small Gtpase ◽  
Cell Cycle Regulators ◽  
Gtpase Activating Protein ◽  
Domain Family ◽  
Protein Motif ◽  
Conserved Domain ◽  
And Function

The TBC (Tre-2/Bub2/Cdc16) domain was originally identified as a conserved domain among the tre-2 oncogene product and the yeast cell cycle regulators Bub2 and Cdc16, and it is now widely recognized as a conserved protein motif that consists of approx. 200 amino acids in all eukaryotes. Since the TBC domain of yeast Gyps [GAP (GTPase-activating protein) for Ypt proteins] has been shown to function as a GAP domain for small GTPase Ypt/Rab, TBC domain-containing proteins (TBC proteins) in other species are also expected to function as a certain Rab-GAP. More than 40 different TBC proteins are present in humans and mice, and recent accumulating evidence has indicated that certain mammalian TBC proteins actually function as a specific Rab-GAP. Some mammalian TBC proteins {e.g. TBC1D1 [TBC (Tre-2/Bub2/Cdc16) domain family, member 1] and TBC1D4/AS160 (Akt substrate of 160 kDa)} play an important role in homoeostasis in mammals, and defects in them are directly associated with mouse and human diseases (e.g. leanness in mice and insulin resistance in humans). The present study reviews the structure and function of mammalian TBC proteins, especially in relation to Rab small GTPases.

Designed Ankyrin Repeat Proteins as Novel Binders for Ultrasound Molecular Imaging

2021 ◽  
Author(s):  
Alexandra Kosareva ◽  
Mukesh Punjabi ◽  
Amanda Ochoa-Espinosa ◽  
Lifen Xu ◽  
Jonas V. Schaefer ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ankyrin Repeat ◽  
Repeat Proteins ◽  
Ultrasound Molecular Imaging ◽  
Ankyrin Repeat Proteins

scholarly journals The proteome: structure, function and evolution

2006 ◽  
Vol 361 (1467) ◽  
pp. 441-451 ◽  
Author(s):  
Keiran Fleming ◽  
Lawrence A Kelley ◽  
Suhail A Islam ◽  
Robert M MacCallum ◽  
Arne Muller ◽  
...  
Keyword(s):  
Protein Function ◽  
Sequence Similarity ◽  
Structural Annotation ◽  
New Approach ◽  
Link Type ◽  
University College London ◽  
Automated Pipeline ◽  
3D Genomics ◽  
And Function ◽  
Structural Homologue

This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk . Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein ( http://www.e-protein.org/ ). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family.

scholarly journals Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs

2021 ◽  
Author(s):  
Johannes Schilling ◽  
Christian Jost ◽  
Ioana Mariuca Ilie ◽  
Joachim Schnabl ◽  
Oralea Buechi ◽  
...  
Keyword(s):  
Melting Temperature ◽  
Building Blocks ◽  
Ankyrin Repeat ◽  
Internal Repeat ◽  
Repeat Proteins ◽  
Repeat Domain ◽  
Ankyrin Repeat Proteins ◽  
Classical Immunoglobulin ◽  
Dynamics Simulations ◽  
Innovative Drugs

AbstractDesigned Ankyrin Repeat Proteins (DARPins) are a class of antibody mimetics with a high and mostly unexplored potential in drug development. They are clinically validated and thus represent a true alternative to classical immunoglobulin formats. In contrast to immunoglobulins, they are built from solenoid protein domains comprising an N-terminal capping repeat, one or more internal repeats and a C-terminal capping repeat. By using in silico analysis and a rationally guided Ala-Scan, we identified position 17 of the N-terminal capping repeat to play a key role for the overall protein thermostability. The melting temperature of a DARPin domain with a single full-consensus internal repeat was increased by about 8°C to 10°C when the original Asp17 was replaced by Leu, Val, Ile, Met, Ala or Thr, as shown by high-temperature unfolding experiments at equilibrium. We then transferred the Asp17Leu mutation to various backgrounds, including different N- and C-terminal capping repeats and clinically validated DARPin domains, such as the VEGF-binding ankyrin repeat domain of abicipar pegol. In all cases, the proteins remained monomeric and showed improvements in the thermostability of about 8°C to 16°C. Thus, the replacement of Asp17 seems to be generically applicable to this drug class. Molecular dynamics simulations show that the Asp17Leu mutation reduces electrostatic repulsion and improves van-der-Waals packing, rendering the DARPin domain less flexible and more stable. Interestingly, such a beneficial Asp17Leu mutation is present in the N-terminal caps of three of the five DARPin domains of ensovibep, a SARS-CoV-2 entry inhibitor currently in clinical development. This mutation is likely responsible, at least in part, for the very high melting temperature (>90°C) of this promising anti-Covid-19 drug. Overall, such N-terminal capping repeats with increased thermostability seem to be beneficial for the development of innovative drugs based on DARPins.

scholarly journals In-silico prediction and observations of nuclear matrix attachment

2006 ◽  
Vol 11 (2) ◽  
Author(s):  
Adrian Platts ◽  
Amelia Quayle ◽  
Stephen Krawetz
Keyword(s):  
Nuclear Matrix ◽  
In Silico ◽  
Sequence Similarity ◽  
Loop Model ◽  
Simple Loop ◽  
Structural Framework ◽  
The Subject ◽  
In Silico Predictions ◽  
The One ◽  
And Function

AbstractThe nuclear matrix is a functionally adaptive structural framework interior to the nuclear envelope. The nature and function of this nuclear organizer remains the subject of widespread discussion in the epigenetic literature. To draw this discussion together with a view to suggest a way forward we summarize the biochemical evidence for the modalities of DNA-matrix binding alongside the in-silico predictions. Concordance is exhibited at various, but not all levels. On the one hand, both the reiteration and sequence similarity of some elements of Matrix Attachment Regions suggest conservation. On the other hand, in-silico predictions suggest additional unique components. In bringing together biological and sequence evidence we conclude that binding may be hierarchical in nature, reflective of a biological role in replicating, transcribing and potentiating chromatin. Nuclear matrix binding may well be more complex than the widely accepted simple loop model.

520YS , Encoding an Ankyrin Repeat Protein, is Involved in Chloroplast Development in Rice

2020 ◽  
Author(s):  
Pingrong Wang ◽  
Fuliang Xiao ◽  
San Wang ◽  
Jia Guo ◽  
Qingsong Liu ◽  
...  
Keyword(s):  
Chloroplast Development ◽  
Protein Translocation ◽  
Sequence Similarity ◽  
Rice Cultivar ◽  
Ankyrin Repeat ◽  
Green Leaf ◽  
Plastid Differentiation ◽  
Mutant Type ◽  
Leaf Phenotype ◽  
Leaf Mutant

Abstract BackgroundThe ankyrin repeat (ANK) proteins are widely distributed in organisms ranging from viruses to plants, which play key roles in plastid differentiation, embryogenesis, chloroplast biogenesis and so on. However, only a few ANK genes have been identified in rice.ResultsIn this study, we isolated a yellow-green leaf mutant, 520ys, from japonica rice cultivar Nipponbare through ethyl methane sulfonate mutagenesis. The mutant exhibited a yellow-green leaf phenotype throughout the life cycle, arrested development of chloroplasts, reduced levels of photosynthetic pigments, and accumulated reactive oxide species. Map-based cloning suggested that the candidate gene was LOC_Os07g33660, which encodes an expressed protein containing one ankyrin repeat and showing sequence similarity with the Arabidopsis LTD/GDC1 (At1g50900). Transgenic complementation experiment confirmed that LOC_Os07g33660 is the causal gene for the mutant type of 520ys. 520YS (LOC_Os07g33660) is mainly expressed in green tissues and its encoded protein is targeted to the chloroplast. In 520ys mutant, expression levels of four light-harvesting chlorophyll a/b-binding protein translocation-related genes and eight photosynthesis-related genes were significantly down-regulated.ConclusionWe characterized a novel ANK gene, 520YS, which plays a key role in chloroplast development in rice.

scholarly journals The role of SCF ubiquitin-ligase complex at the beginning of life

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiayan Xie ◽  
Yimei Jin ◽  
Guang Wang
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cellular Proteins ◽  
Cell Cycle Regulators ◽  
Signal Transducers ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin Ligase Complex ◽  
Scf Ubiquitin Ligase

AbstractAs the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.

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