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hfAIM: a reliable bioinformatics approach for in silico genome-wide identification of autophagy-associated Atg8-interacting motifs in various organisms

Qingjun Xie, Oren Tzfadia UGent, Matan Levy, Efrat Weithorn, Hadas Peled-Zehavi, Thomas Van Parys UGent, Yves Van de Peer UGent and Gad Galili (2016) AUTOPHAGY. 12(5). p.876-887
abstract
Most of the proteins that are specifically turned over by selective autophagy are recognized by the presence of short Atg8 interacting motifs (AIMs) that facilitate their association with the autophagy apparatus. Such AIMs can be identified by bioinformatics methods based on their defined degenerate consensus F/W/Y-X-X-L/I/V sequences in which X represents any amino acid. Achieving reliability and/or fidelity of the prediction of such AIMs on a genome-wide scale represents a major challenge. Here, we present a bioinformatics approach, high fidelity AIM (hfAIM), which uses additional sequence requirementsthe presence of acidic amino acids and the absence of positively charged amino acids in certain positionsto reliably identify AIMs in proteins. We demonstrate that the use of the hfAIM method allows for in silico high fidelity prediction of AIMs in AIM-containing proteins (ACPs) on a genome-wide scale in various organisms. Furthermore, by using hfAIM to identify putative AIMs in the Arabidopsis proteome, we illustrate a potential contribution of selective autophagy to various biological processes. More specifically, we identified 9 peroxisomal PEX proteins that contain hfAIM motifs, among which AtPEX1, AtPEX6 and AtPEX10 possess evolutionary-conserved AIMs. Bimolecular fluorescence complementation (BiFC) results verified that AtPEX6 and AtPEX10 indeed interact with Atg8 in planta. In addition, we show that mutations occurring within or nearby hfAIMs in PEX1, PEX6 and PEX10 caused defects in the growth and development of various organisms. Taken together, the above results suggest that the hfAIM tool can be used to effectively perform genome-wide in silico screens of proteins that are potentially regulated by selective autophagy. The hfAIM system is a web tool that can be accessed at link: http://bioinformatics.psb.ugent.be/hfAIM/.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CARBON STARVATION, ARABIDOPSIS PEX10, PLANT PEROXISOMES, SELECTIVE AUTOPHAGY, ZINC RING FINGER, MATRIX PROTEIN-DEGRADATION, pexophagy, PEX, bioinformatics, autophagy, Arabidopsis, Atg8, AIM, MUTANT, SYSTEM, METABOLISM, RECOGNITION
journal title
AUTOPHAGY
Autophagy
volume
12
issue
5
pages
876 - 887
Web of Science type
Article
Web of Science id
000375330100010
JCR category
CELL BIOLOGY
JCR impact factor
8.593 (2016)
JCR rank
22/189 (2016)
JCR quartile
1 (2016)
ISSN
1554-8627
DOI
10.1080/15548627.2016.1147668
project
Bioinformatics: from nucleotids to networks (N2N)
language
English
UGent publication?
yes
classification
A1
additional info
the first two authors contributed equally to this manuscript
copyright statement
I have transferred the copyright for this publication to the publisher
id
7244278
handle
http://hdl.handle.net/1854/LU-7244278
date created
2016-06-06 13:21:09
date last changed
2016-12-19 15:39:11
@article{7244278,
  abstract     = {Most of the proteins that are specifically turned over by selective autophagy are recognized by the presence of short Atg8 interacting motifs (AIMs) that facilitate their association with the autophagy apparatus. Such AIMs can be identified by bioinformatics methods based on their defined degenerate consensus F/W/Y-X-X-L/I/V sequences in which X represents any amino acid. Achieving reliability and/or fidelity of the prediction of such AIMs on a genome-wide scale represents a major challenge. Here, we present a bioinformatics approach, high fidelity AIM (hfAIM), which uses additional sequence requirementsthe presence of acidic amino acids and the absence of positively charged amino acids in certain positionsto reliably identify AIMs in proteins. We demonstrate that the use of the hfAIM method allows for in silico high fidelity prediction of AIMs in AIM-containing proteins (ACPs) on a genome-wide scale in various organisms. Furthermore, by using hfAIM to identify putative AIMs in the Arabidopsis proteome, we illustrate a potential contribution of selective autophagy to various biological processes. More specifically, we identified 9 peroxisomal PEX proteins that contain hfAIM motifs, among which AtPEX1, AtPEX6 and AtPEX10 possess evolutionary-conserved AIMs. Bimolecular fluorescence complementation (BiFC) results verified that AtPEX6 and AtPEX10 indeed interact with Atg8 in planta. In addition, we show that mutations occurring within or nearby hfAIMs in PEX1, PEX6 and PEX10 caused defects in the growth and development of various organisms. Taken together, the above results suggest that the hfAIM tool can be used to effectively perform genome-wide in silico screens of proteins that are potentially regulated by selective autophagy. The hfAIM system is a web tool that can be accessed at link: http://bioinformatics.psb.ugent.be/hfAIM/.},
  author       = {Xie, Qingjun and Tzfadia, Oren and Levy, Matan and Weithorn, Efrat and Peled-Zehavi, Hadas and Van Parys, Thomas and Van de Peer, Yves and Galili, Gad},
  issn         = {1554-8627},
  journal      = {AUTOPHAGY},
  keyword      = {CARBON STARVATION,ARABIDOPSIS PEX10,PLANT PEROXISOMES,SELECTIVE AUTOPHAGY,ZINC RING FINGER,MATRIX PROTEIN-DEGRADATION,pexophagy,PEX,bioinformatics,autophagy,Arabidopsis,Atg8,AIM,MUTANT,SYSTEM,METABOLISM,RECOGNITION},
  language     = {eng},
  number       = {5},
  pages        = {876--887},
  title        = {hfAIM: a reliable bioinformatics approach for in silico genome-wide identification of autophagy-associated Atg8-interacting motifs in various organisms},
  url          = {http://dx.doi.org/10.1080/15548627.2016.1147668},
  volume       = {12},
  year         = {2016},
}

Chicago
Xie, Qingjun, Oren Tzfadia, Matan Levy, Efrat Weithorn, Hadas Peled-Zehavi, Thomas Van Parys, Yves Van de Peer, and Gad Galili. 2016. “hfAIM: a Reliable Bioinformatics Approach for in Silico Genome-wide Identification of Autophagy-associated Atg8-interacting Motifs in Various Organisms.” Autophagy 12 (5): 876–887.
APA
Xie, Qingjun, Tzfadia, O., Levy, M., Weithorn, E., Peled-Zehavi, H., Van Parys, T., Van de Peer, Y., et al. (2016). hfAIM: a reliable bioinformatics approach for in silico genome-wide identification of autophagy-associated Atg8-interacting motifs in various organisms. AUTOPHAGY, 12(5), 876–887.
Vancouver
1.
Xie Q, Tzfadia O, Levy M, Weithorn E, Peled-Zehavi H, Van Parys T, et al. hfAIM: a reliable bioinformatics approach for in silico genome-wide identification of autophagy-associated Atg8-interacting motifs in various organisms. AUTOPHAGY. 2016;12(5):876–87.
MLA
Xie, Qingjun, Oren Tzfadia, Matan Levy, et al. “hfAIM: a Reliable Bioinformatics Approach for in Silico Genome-wide Identification of Autophagy-associated Atg8-interacting Motifs in Various Organisms.” AUTOPHAGY 12.5 (2016): 876–887. Print.