Getting into mitochondria

2016 ◽  
Vol 473 (21) ◽  
pp. 3755-3758 ◽  
Author(s):  
Ján A. Miernyk
Keyword(s):  
Secondary Structure ◽  
Glutamate Dehydrogenase ◽  
Protein Import ◽  
Terminal Region ◽  
Nuclear Genes ◽  
Cleavage Sites ◽  
Mitochondrial Targeting ◽  
Limited Ability ◽  
Secondary Structure Predictions ◽  
High Matrix

The human mitochondrial glutamate dehydrogenase isoenzymes (hGDH1 and hGDH2) are abundant matrix-localized proteins encoded by nuclear genes. The proteins are synthesized in the cytoplasm, with an atypically long N-terminal mitochondrial targeting sequence (MTS). The results of secondary structure predictions suggest the presence of two α-helices within the N-terminal region of the MTS. Results from deletion analyses indicate that individual helices have limited ability to direct protein import and matrix localization, but that there is a synergistic interaction when both helices are present [Biochem. J. (2016) 473, 2813–2829]. Mutagenesis of the MTS cleavage sites blocked post-import removal of the presequences, but did not impede import. The authors propose that the high matrix levels of hGDH can be attributed to the unusual length and secondary structure of the MTS.

scholarly journals Strawberry Mottle Virus (Family Secoviridae, Order Picornavirales) Encodes a Novel Glutamic Protease To Process the RNA2 Polyprotein at Two Cleavage Sites

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Krin S. Mann ◽  
Joan Chisholm ◽  
Hélène Sanfaçon
Keyword(s):  
Cysteine Proteases ◽  
Terminal Region ◽  
Mottle Virus ◽  
Cleavage Sites ◽  
Virus Family ◽  
Positive Strand ◽  
Viral Proteases ◽  
Bipartite Genome ◽  
The Family ◽  
Positive Strand Rna

ABSTRACT Strawberry mottle virus (SMoV) belongs to the family Secoviridae (order Picornavirales) and has a bipartite genome with each RNA encoding one polyprotein. All characterized secovirids encode a single protease related to the picornavirus 3C protease. The SMoV 3C-like protease was previously shown to cut the RNA2 polyprotein (P2) at a single site between the predicted movement protein and coat protein (CP) domains. However, the SMoV P2 polyprotein includes an extended C-terminal region with a coding capacity of up to 70 kDa downstream of the presumed CP domain, an unusual characteristic for this family. In this study, we identified a novel cleavage event at a P↓AFP sequence immediately downstream of the CP domain. Following deletion of the PAFP sequence, the polyprotein was processed at or near a related PKFP sequence 40 kDa further downstream, defining two protein domains in the C-terminal region of the P2 polyprotein. Both processing events were dependent on a novel protease domain located between the two cleavage sites. Mutagenesis of amino acids that are conserved among isolates of SMoV and of the related Black raspberry necrosis virus did not identify essential cysteine, serine, or histidine residues, suggesting that the RNA2-encoded SMoV protease is not related to serine or cysteine proteases of other picorna-like viruses. Rather, two highly conserved glutamic acid residues spaced by 82 residues were found to be strictly required for protease activity. We conclude that the processing of SMoV polyproteins requires two viral proteases, the RNA1-encoded 3C-like protease and a novel glutamic protease encoded by RNA2. IMPORTANCE Many viruses encode proteases to release mature proteins and intermediate polyproteins from viral polyproteins. Polyprotein processing allows regulation of the accumulation and activity of viral proteins. Many viral proteases also cleave host factors to facilitate virus infection. Thus, viral proteases are key virulence factors. To date, viruses with a positive-strand RNA genome are only known to encode cysteine or serine proteases, most of which are related to the cellular papain, trypsin, or chymotrypsin proteases. Here, we characterize the first glutamic protease encoded by a plant virus or by a positive-strand RNA virus. The novel glutamic protease is unique to a few members of the family Secoviridae, suggesting that it is a recent acquisition in the evolution of this family. The protease does not resemble known cellular proteases. Rather, it is predicted to share structural similarities with a family of fungal and bacterial glutamic proteases that adopt a lectin fold.

Plasticity of secondary structure in the N-terminal region of β-dystroglycan

2001 ◽  
Vol 1546 (1) ◽  
pp. 114-121 ◽  
Author(s):  
Alberto Boffi ◽  
Manuela Bozzi ◽  
Francesca Sciandra ◽  
Cristina Woellner ◽  
Maria Giulia Bigotti ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Terminal Region

Analysis of X-Ray Scattering by Human AA Fibrils Using Secondary Structure Predictions of Human SAA1

Amyloidosis ◽  
1986 ◽  
pp. 49-55 ◽  
Author(s):  
W. G. Turnell ◽  
R. Sarra ◽  
I. D. Glover ◽  
J. O. Baum ◽  
D. Caspi ◽  
...  
Keyword(s):  
Secondary Structure ◽  
X Ray ◽  
X Ray Scattering ◽  
Secondary Structure Predictions ◽  
Ray Scattering

CARBOHYDRATE PREVENTS LOSS OF LARGE VON WILLEBRAND FACTOR MULTIMERS BY PROTECTING AGAINST AMINO TERMINAL PROTEOLYTIC CLEAVAGE

1987 ◽  
Author(s):  
A B Federici ◽  
S D Berkowitz
Keyword(s):  
Von Willebrand Factor ◽  
Proteinase Inhibitors ◽  
Enzymatic Digestion ◽  
Terminal Region ◽  
Cleavage Sites ◽  
Amino Terminal ◽  
Carboxy Terminal ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

We have previously shown that carbohydrate (CHO) protects von Willebrand factor (vWF) from proteolytic degradation. We have now shown that removal of CHO from the vWF subunit exposes additional cleavage sites in the amino terminal region and that cleavages in this region are associated with loss of large multimers. We examined and compared the extent of large multimer loss with sites of subunit cleavage of native and GHO-modified vWF after treatment with plasmin, chymotrypsin, and trypsin. Highly purified vWF was treated with neuraminidase and β-galactosidase in the presence of proteinase inhibitors to remove 90-95% of the sialic acid and 45-50% of the D-galactose without loss of large multimers or diminution of the ristocetin cofactor activity. The extent and approximate location of subunit cleavage was determined by immunoblotting and monoclonal antibody epitope mapping. Multimeric analysis revealed an increasingly greater loss of large multimers when native vWF was digested with plasmin, chymotrypsin, and trypsin, respectively. Large multimer loss was more extensive with each enzyme after CHO-modification of vWF. On subunit analysis, plasmin, chymotrypsin, and trypsin were shown to produce both amino and carboxy terminal fragments. The number, location, and relative quantities of carboxy terminal fragments produced by these enzymes were unchanged after CHO modification. However, digestion of the amino terminal region was considerably more extensive as judged by a marked decrease or absence of the larger fragments seen when native vWF was digested, and by the appearance of new smaller molecular weight species. Thus, enzymatic digestion of vWF after removal of carbohydrate produced new cleavages in the amino terminal region but did not alter the location or extent of carboxy terminal cleavages. Therefore, the greater loss of large multimers that occurs after CHO modification is likely to be the result of cleavages in the amino terminal region of the molecule. It appears that by protecting the vWF subunit against amino terminal cleavage, carbohydrate inhibits the loss of large multimers.

Involvement of N-terminal region in mitochondrial targeting of rice RPS10 and RPS14 proteins

Plant Science ◽  
2003 ◽  
Vol 164 (6) ◽  
pp. 1047-1055 ◽  
Author(s):  
Nakao Kubo ◽  
Shin-ichi Arimura ◽  
Nobuhiro Tsutsumi ◽  
Atsushi Hirai ◽  
Koh-ichi Kadowaki
Keyword(s):  
Terminal Region ◽  
Mitochondrial Targeting

A sequence-based approach for identifying protein fold switchers

2018 ◽  
Author(s):  
Soumya Mishra ◽  
Loren L. Looger ◽  
Lauren L. Porter
Keyword(s):  
Secondary Structure ◽  
Drug Targets ◽  
Prediction Method ◽  
Data Bank ◽  
Amino Acid Sequences ◽  
Protein Fold ◽  
Secondary Structure Predictions ◽  
Underlying Mechanisms ◽  
Cellular Control ◽  
Potential Drug Targets

AbstractAlthough most proteins conform to the classical one-structure/one-function paradigm, an increasing number of proteins with dual structures and functions are emerging. These fold-switching proteins remodel their secondary structures in response to cellular stimuli, fostering multi-functionality and tight cellular control. Accurate predictions of fold-switching proteins could both suggest underlying mechanisms for uncharacterized biological processes and reveal potential drug targets. Previously, we developed a prediction method for fold-switching proteins based on secondary structure predictions and structure-based thermodynamic calculations. Given the large number of genomic sequences without homologous experimentally characterized structures, however, we sought to predict fold-switching proteins from their sequences alone. To do this, we leveraged state-of-the-art secondary structure predictions, which require only amino acid sequences but are not currently designed to identify structural duality in proteins. Thus, we hypothesized that incorrect and inconsistent secondary structure predictions could be good initial predictors of fold-switching proteins. We found that secondary structure predictions of fold-switching proteins with solved structures are indeed less accurate than secondary structure predictions of non-fold-switching proteins with solved structures. These inaccuracies result largely from the conformations of fold-switching proteins that are underrepresented in the Protein Data Bank (PDB), and, consequently, the training sets of secondary structure predictors. Given that secondary structure predictions are homology-based, we hypothesized that decontextualizing the inaccurately-predicted regions of fold-switching proteins could weaken the homology relationships between these regions and their overpopulated structural representatives. Thus, we reran secondary structure predictions on these regions in isolation and found that they were significantly more inconsistent than in regions of non-fold-switching proteins. Thus, inconsistent secondary structure predictions can serve as a preliminary marker of fold switching. These findings have implications for genomics and the future development of secondary structure predictors.

scholarly journals OPUS-TASS: a protein backbone torsion angles and secondary structure predictor based on ensemble neural networks

2020 ◽  
Vol 36 (20) ◽  
pp. 5021-5026 ◽  
Author(s):  
Gang Xu ◽  
Qinghua Wang ◽  
Jianpeng Ma
Keyword(s):  
Neural Networks ◽  
Secondary Structure ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Supplementary Information ◽  
Learning Approaches ◽  
Protein Backbone ◽  
Torsion Angles ◽  
Secondary Structure Predictions ◽  
The Mean

Abstract Motivation Predictions of protein backbone torsion angles (ϕ and ψ) and secondary structure from sequence are crucial subproblems in protein structure prediction. With the development of deep learning approaches, their accuracies have been significantly improved. To capture the long-range interactions, most studies integrate bidirectional recurrent neural networks into their models. In this study, we introduce and modify a recently proposed architecture named Transformer to capture the interactions between the two residues theoretically with arbitrary distance. Moreover, we take advantage of multitask learning to improve the generalization of neural network by introducing related tasks into the training process. Similar to many previous studies, OPUS-TASS uses an ensemble of models and achieves better results. Results OPUS-TASS uses the same training and validation sets as SPOT-1D. We compare the performance of OPUS-TASS and SPOT-1D on TEST2016 (1213 proteins) and TEST2018 (250 proteins) proposed in the SPOT-1D paper, CASP12 (55 proteins), CASP13 (32 proteins) and CASP-FM (56 proteins) proposed in the SAINT paper, and a recently released PDB structure collection from CAMEO (93 proteins) named as CAMEO93. On these six test sets, OPUS-TASS achieves consistent improvements in both backbone torsion angles prediction and secondary structure prediction. On CAMEO93, SPOT-1D achieves the mean absolute errors of 16.89 and 23.02 for ϕ and ψ predictions, respectively, and the accuracies for 3- and 8-state secondary structure predictions are 87.72 and 77.15%, respectively. In comparison, OPUS-TASS achieves 16.56 and 22.56 for ϕ and ψ predictions, and 89.06 and 78.87% for 3- and 8-state secondary structure predictions, respectively. In particular, after using our torsion angles refinement method OPUS-Refine as the post-processing procedure for OPUS-TASS, the mean absolute errors for final ϕ and ψ predictions are further decreased to 16.28 and 21.98, respectively. Availability and implementation The training and the inference codes of OPUS-TASS and its data are available at https://github.com/thuxugang/opus_tass. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Inaccurate secondary structure predictions often indicate protein fold switching

2019 ◽  
Vol 28 (8) ◽  
pp. 1487-1493 ◽  
Author(s):  
Soumya Mishra ◽  
Loren L. Looger ◽  
Lauren L. Porter
Keyword(s):  
Secondary Structure ◽  
Protein Fold ◽  
Secondary Structure Predictions
Sign in / Sign up

Export Citation Format

Share Document