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N-terminal proteoforms may engage in different protein complexes

Bogaert, Annelies (author)
VIB Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
Fijalkowska, Daria (author)
VIB Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
Staes, An (author)
VIB Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
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Van de Steene, Tessa (author)
VIB Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
Vuylsteke, Marnik (author)
Gnomixx, Melle, Belgium
Stadler, Charlotte (author)
KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap
Eyckerman, Sven (author)
VIB Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
Spirohn, Kerstin (author)
Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA
Hao, Tong (author)
Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA
Calderwood, Michael A. (author)
Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA
Gevaert, Kris (author)
VIB Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
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 (creator_code:org_t)
Life Science Alliance, LLC, 2023
2023
English.
In: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 6:8
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  • Journal article (peer-reviewed)
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  • Alternative translation initiation and alternative splicing may give rise to N-terminal proteoforms, proteins that differ at their N-terminus compared with their canonical counterparts. Such proteoforms can have altered localizations, stabilities, and functions. Although proteoforms generated from splice variants can be engaged in different protein complexes, it remained to be studied to what extent this applies to N-terminal proteoforms. To address this, we mapped the interactomes of several pairs of N-terminal proteoforms and their canonical counterparts. First, we generated a catalogue of N-terminal proteoforms found in the HEK293T cellular cytosol from which 22 pairs were selected for interactome profiling. In addition, we provide evidence for the expression of several N-terminal proteoforms, identified in our catalogue, across different human tissues, as well as tissue-specific expression, highlighting their biological relevance. Protein–protein interaction profiling revealed that the overlap of the interactomes for both proteoforms is generally high, showing their functional relation. We also showed that N-terminal proteoforms can be engaged in new interactions and/or lose several interactions compared with their canonical counterparts, thus further expanding the functional diversity of proteomes.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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