scholarly journals Identification of Intrinsically Disordered Protein Regions Based on Deep Neural Network-VGG16

Algorithms ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 107
Author(s):  
Pengchang Xu ◽  
Jiaxiang Zhao ◽  
Jie Zhang
Keyword(s):  
Neural Network ◽  
Deep Neural Network ◽  
Biological Process ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Blind Test ◽  
Test Set ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Trained Neural Network

The accurate of i identificationntrinsically disordered proteins or protein regions is of great importance, as they are involved in critical biological process and related to various human diseases. In this paper, we develop a deep neural network that is based on the well-known VGG16 . Our deep neural network is then trained through using 1450 proteins from the dataset DIS1616 and the trained neural network is tested on the remaining 166 proteins. Our trained neural network is also tested on the blind test set R80 and MXD494 to further demonstrate the performance of our model. The MCC value of our trained deep neural network is 0.5132 on the test set DIS166, 0.5270 on the blind test set R80 and 0.4577 on the blind test set MXD494. All of these MCC values of our trained deep neural network exceed the corresponding values of existing prediction methods.

scholarly journals The Contribution of the 20S Proteasome to Proteostasis

Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 190 ◽  
Author(s):  
Fanindra Kumar Deshmukh ◽  
Dana Yaffe ◽  
Maya Olshina ◽  
Gili Ben-Nissan ◽  
Michal Sharon
Keyword(s):  
Biological Process ◽  
Intrinsically Disordered Protein ◽  
26S Proteasome ◽  
20S Proteasome ◽  
Biological Processes ◽  
Neuronal Communication ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
The Core ◽  
Functional Aspects

The last decade has seen accumulating evidence of various proteins being degraded by the core 20S proteasome, without its regulatory particle(s). Here, we will describe recent advances in our knowledge of the functional aspects of the 20S proteasome, exploring several different systems and processes. These include neuronal communication, post-translational processing, oxidative stress, intrinsically disordered protein regulation, and extracellular proteasomes. Taken together, these findings suggest that the 20S proteasome, like the well-studied 26S proteasome, is involved in multiple biological processes. Clarifying our understanding of its workings calls for a transformation in our perception of 20S proteasome-mediated degradation—no longer as a passive and marginal path, but rather as an independent, coordinated biological process. Nevertheless, in spite of impressive progress made thus far, the field still lags far behind the front lines of 26S proteasome research. Therefore, we also touch on the gaps in our knowledge of the 20S proteasome that remain to be bridged in the future.

scholarly journals New technologies to analyse protein function: an intrinsic disorder perspective

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 101 ◽  
Author(s):  
Vladimir N. Uversky
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Proteins ◽  
New Technologies ◽  
Intrinsically Disordered Protein ◽  
Intrinsic Disorder ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Protein Functions ◽  
Require Structure

Functions of intrinsically disordered proteins do not require structure. Such structure-independent functionality has melted away the classic rigid “lock and key” representation of structure–function relationships in proteins, opening a new page in protein science, where molten keys operate on melted locks and where conformational flexibility and intrinsic disorder, structural plasticity and extreme malleability, multifunctionality and binding promiscuity represent a new-fangled reality. Analysis and understanding of this new reality require novel tools, and some of the techniques elaborated for the examination of intrinsically disordered protein functions are outlined in this review.

scholarly journals DEEP picker is a deep neural network for accurate deconvolution of complex two-dimensional NMR spectra

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Da-Wei Li ◽  
Alexandar L. Hansen ◽  
Chunhua Yuan ◽  
Lei Bruschweiler-Li ◽  
Rafael Brüschweiler
Keyword(s):  
Neural Network ◽  
Nmr Spectra ◽  
Deep Neural Network ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Two Dimensional ◽  
Molecular Systems ◽  
Intrinsically Disordered ◽  
Identification And Characterization

AbstractThe analysis of nuclear magnetic resonance (NMR) spectra for the comprehensive and unambiguous identification and characterization of peaks is a difficult, but critically important step in all NMR analyses of complex biological molecular systems. Here, we introduce DEEP Picker, a deep neural network (DNN)-based approach for peak picking and spectral deconvolution which semi-automates the analysis of two-dimensional NMR spectra. DEEP Picker includes 8 hidden convolutional layers and was trained on a large number of synthetic spectra of known composition with variable degrees of crowdedness. We show that our method is able to correctly identify overlapping peaks, including ones that are challenging for expert spectroscopists and existing computational methods alike. We demonstrate the utility of DEEP Picker on NMR spectra of folded and intrinsically disordered proteins as well as a complex metabolomics mixture, and show how it provides access to valuable NMR information. DEEP Picker should facilitate the semi-automation and standardization of protocols for better consistency and sharing of results within the scientific community.

scholarly journals Phosphorylation regulates the binding of intrinsically disordered proteins via a flexible conformation selection mechanism

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Na Liu ◽  
Yue Guo ◽  
Shangbo Ning ◽  
Mojie Duan
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Hydrophobic Interactions ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Regulation Mechanism ◽  
Enhanced Sampling ◽  
Dynamic Interactions ◽  
Post Translational Modifications ◽  
Intrinsically Disordered ◽  
Disordered Protein

Abstract Phosphorylation is one of the most common post-translational modifications. The phosphorylation of the kinase-inducible domain (KID), which is an intrinsically disordered protein (IDP), promotes the folding of KID and binding with the KID-interacting domain (KIX). However, the regulation mechanism of the phosphorylation on KID is still elusive. In this study, the structural ensembles and binding process of pKID and KIX are studied by all-atom enhanced sampling technologies. The results show that more hydrophobic interactions are formed in pKID, which promote the formation of the special hydrophobic residue cluster (HRC). The pre-formed HRC promotes binding to the correct sites of KIX and further lead the folding of pKID. Consequently, a flexible conformational selection model is proposed to describe the binding and folding process of intrinsically disordered proteins. The binding mechanism revealed in this work provides new insights into the dynamic interactions and phosphorylation regulation of proteins.

scholarly journals Kinetic coherence underlies the dynamics of disordered proteins

RSC Advances ◽  
2021 ◽  
Vol 11 (57) ◽  
pp. 36242-36249
Author(s):  
Alexander Tenenbaum
Keyword(s):  
Phase Space ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Structural Coherence

In the phase space of a globular or intrinsically disordered protein, the momenta's dynamics is less chaotic than the coordinates' dynamics. When a protein is denaturated, a gain in kinetic coherence accompanies the loss of structural coherence.

scholarly journals The intrinsically disordered protein SPE-18 promotes localized assembly of the major sperm protein in C. elegans spermatocytes

2020 ◽  
Author(s):  
Kari L. Price ◽  
Marc Presler ◽  
Christopher M. Uyehara ◽  
Diane C. Shakes
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Major Sperm Protein ◽  
Sperm Protein ◽  
C Elegans ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Changing Patterns ◽  
Cytoskeletal Elements

ABSTRACTMany specialized cells use unconventional strategies of cytoskeletal control. Nematode spermatocytes discard their actin and tubulin following meiosis, and instead employ the regulated assembly/disassembly of the Major Sperm Protein (MSP) to drive sperm motility. However prior to the meiotic divisions, MSP is effectively sequestered as it exclusively assembles into paracrystalline structures called fibrous bodies (FBs). The accessory proteins that direct this sequestration process have remained mysterious. This study reveals SPE-18 as an intrinsically disordered protein that that is essential for MSP assembly within FBs. In spe-18 mutant spermatocytes, MSP remains cytosolic, and the cells arrest in meiosis. In wildtype spermatocytes, SPE-18 localizes to pre-FB complexes and functions with the kinase SPE-6 to recruit MSP. Changing patterns of SPE-18 localization revealed unappreciated complexities in FB maturation. Later, within newly individualized spermatids, SPE −18 is rapidly lost, yet SPE-18 loss alone is insufficient for MSP disassembly. Our findings reveal an alternative strategy for sequestering cytoskeletal elements, not as monomers but in localized, bundled polymers. Additionally, these studies provide an important example of disordered proteins promoting ordered cellular structures.Summary StatementIntrinsically disordered proteins are increasingly recognized as key regulators of localized cytoskeletal assembly. Expanding that paradigm, SPE-18 localizes MSP assembly within C. elegans spermatocytes.

scholarly journals Degradation of Intrinsically Disordered Proteins by the NADH 26S Proteasome

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1642
Author(s):  
Peter Tsvetkov ◽  
Nadav Myers ◽  
Julia Adler ◽  
Yosef Shaul
Keyword(s):  
Substrate Specificity ◽  
Structural Integrity ◽  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Degradation Pathway ◽  
26S Proteasome ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Disordered Protein

The 26S proteasome is the endpoint of the ubiquitin- and ATP-dependent degradation pathway. Over the years, ATP was regarded as completely essential for 26S proteasome function due to its role in ubiquitin-signaling, substrate unfolding and ensuring its structural integrity. We have previously reported that physiological concentrations of NADH are efficient in replacing ATP to maintain the integrity of an enzymatically functional 26S PC. However, the substrate specificity of the NADH-stabilized 26S proteasome complex (26S PC) was never assessed. Here, we show that the binding of NADH to the 26S PC inhibits the ATP-dependent and ubiquitin-independent degradation of the structured ODC enzyme. Moreover, the NADH-stabilized 26S PC is efficient in degrading intrinsically disordered protein (IDP) substrates that might not require ATP-dependent unfolding, such as p27, Tau, c-Fos and more. In some cases, NADH-26S proteasomes were more efficient in processing IDPs than the ATP-26S PC. These results indicate that in vitro, physiological concentrations of NADH can alter the processivity of ATP-dependent 26S PC substrates such as ODC and, more importantly, the NADH-stabilized 26S PCs promote the efficient degradation of many IDPs. Thus, ATP-independent, NADH-dependent 26S proteasome activity exemplifies a new principle of how mitochondria might directly regulate 26S proteasome substrate specificity.

scholarly journals The intrinsically disordered protein SPE-18 promotes localized assembly of MSP in Caenorhabditis elegans spermatocytes

Development ◽  
2021 ◽  
Vol 148 (5) ◽  
pp. dev195875
Author(s):  
Kari L. Price ◽  
Marc Presler ◽  
Christopher M. Uyehara ◽  
Diane C. Shakes
Keyword(s):  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Cellular Structures ◽  
Major Sperm Protein ◽  
Wild Type ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Changing Patterns ◽  
Cortical Fibers ◽  
Cytoskeletal Elements

ABSTRACTMany specialized cells use unconventional strategies of cytoskeletal control. Nematode spermatocytes discard their actin and tubulin following meiosis, and instead employ the regulated assembly/disassembly of the Major Sperm Protein (MSP) to drive sperm motility. However, prior to the meiotic divisions, MSP is sequestered through its assembly into paracrystalline structures called fibrous bodies (FBs). The accessory proteins that direct this sequestration process have remained mysterious. This study reveals SPE-18 as an intrinsically disordered protein that is essential for MSP assembly within FBs. In spe-18 mutant spermatocytes, MSP forms disorganized cortical fibers, and the cells arrest in meiosis without forming haploid sperm. In wild-type spermatocytes, SPE-18 localizes to pre-FB complexes and functions with the kinase SPE-6 to localize MSP assembly. Changing patterns of SPE-18 localization uncover previously unappreciated complexities in FB maturation. Later, within newly individualized spermatids, SPE-18 is rapidly lost, yet SPE-18 loss alone is insufficient for MSP disassembly. Our findings reveal an alternative strategy for sequestering cytoskeletal elements, not as monomers but in localized, bundled polymers. Additionally, these studies provide an important example of disordered proteins promoting ordered cellular structures.

scholarly journals Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution

2020 ◽  
Vol 6 (30) ◽  
pp. eaba3916 ◽  
Author(s):  
T. Ukmar-Godec ◽  
P. Fang ◽  
A. Ibáñez de Opakua ◽  
F. Henneberg ◽  
A. Godec ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Degradation Products ◽  
Degradation Kinetics ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Dependent Protein Kinase ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Dependent Protein ◽  
Independent Process

Intrinsically disordered proteins (IDPs) can be degraded in a ubiquitin-independent process by the 20S proteasome. Decline in 20S activity characterizes neurodegenerative diseases. Here, we examine 20S degradation of IDP tau, a protein that aggregates into insoluble deposits in Alzheimer’s disease. We show that cleavage of tau by the 20S proteasome is most efficient within the aggregation-prone repeat region of tau and generates both short, aggregation-deficient peptides and two long fragments containing residues 1 to 251 and 1 to 218. Phosphorylation of tau by the non-proline–directed Ca2+/calmodulin-dependent protein kinase II inhibits degradation by the 20S proteasome. Phosphorylation of tau by GSK3β, a major proline-directed tau kinase, modulates tau degradation kinetics in a residue-specific manner. The study provides detailed insights into the degradation products of tau generated by the 20S proteasome, the residue specificity of degradation, single-residue degradation kinetics, and their regulation by posttranslational modification.

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