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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
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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/.
Keywords
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

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Citation

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MLA
Xie, Qingjun, et al. “HfAIM: A Reliable Bioinformatics Approach for in Silico Genome-Wide Identification of Autophagy-Associated Atg8-Interacting Motifs in Various Organisms.” AUTOPHAGY, vol. 12, no. 5, 2016, pp. 876–87, doi:10.1080/15548627.2016.1147668.
APA
Xie, Q., Tzfadia, O., Levy, M., Weithorn, E., Peled-Zehavi, H., Van Parys, T., … Galili, G. (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. https://doi.org/10.1080/15548627.2016.1147668
Chicago author-date
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): 876–87. https://doi.org/10.1080/15548627.2016.1147668.
Chicago author-date (all authors)
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. doi:10.1080/15548627.2016.1147668.
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.
IEEE
[1]
Q. Xie et al., “hfAIM: a reliable bioinformatics approach for in silico genome-wide identification of autophagy-associated Atg8-interacting motifs in various organisms,” AUTOPHAGY, vol. 12, no. 5, pp. 876–887, 2016.
@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}},
  keywords     = {{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}},
}
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