A Conserved Proline in the Last Transmembrane Segment of Gaa1 Is Required for Glycosylphosphatidylinositol (GPI) Recognition by GPI Transamidase
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Glycosylphosphatidylinositol (GPI)-anchored proteins are synthesized as precursor proteins that are processed in the endoplasmic reticulum by GPI transamidase (GPIT). Human GPIT is a multisubunit membrane-bound protein complex consisting of Gaa1, Gpi8, phosphatidylinositol glycan (PIG)-S, PIG-T, and PIG-U. The enzyme recognizes a C-terminal signal sequence in the proprotein and replaces it with a preformed GPI lipid. The nature of the functional interaction of the GPIT subunits with each other and with the proprotein and GPI substrates is largely unknown. We recently analyzed the GPIT subunit Gaa1, a polytopic protein with seven transmembrane (TM) spans, to identify sequence determinants in the protein that are required for its interaction with other subunits and for function (Vainauskas, S., Maeda, Y., Kurniawan, H., Kinoshita, T., and Menon, A. K. (2002) J. Biol. Chem. 277, 30535-30542). We showed that elimination of the C-terminal TM segment of Gaa1 allows the protein to interact with Gpi8, PIG-S, and PIG-T but renders the resulting GPIT complex nonfunctional. We now show that GPIT complexes containing C-terminally truncated Gaa1 possess a full complement of subunits and are able to interact with a proprotein substrate but cannot co-immunoprecipitate GPI. We go on to show that mutation of a conserved proline residue centrally located within the C-terminal TM span of Gaa1 is sufficient to abrogate the ability of the resulting GPIT complex to co-immunoprecipitate GPI. We suggest that the putative dynamic hinge created by the proline residue provides a structural basis for the interaction of GPI with GPIT.
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Gaa1 is essential for binding of the GPI anchor to GPI-T.
“Gaa1 is essential for binding of the GPI anchor to GPI-T (95)”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [95]
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- Authors
- Vainauskas, S., & Menon, A. K.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Vainauskas, Saulius
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 279
- Issue
- 8
- Pages
- 6540-6545
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2107752085
- Cited by
- 34
- References
- 28
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 3 · 2017: 3 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM055427, GM 55427)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- glycosylphosphatidylinositol anchoring, protein-protein interaction, GPI-anchored proteins
- MeSH terms
- Acyltransferases, Amino Acid Sequence, Animals, Flow Cytometry, HeLa Cells, Hexosaminidases, Humans, Mannose, Membrane Glycoproteins, Molecular Sequence Data, Mutation, Precipitin Tests, Proline, Protein Binding, Transfection, Conserved Sequence, Point Mutation, Sequence Homology, Amino Acid, Protein Structure, Tertiary, DNA, Complementary, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase, Mice
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