Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins
Open accessAbstract
FYCO1 (FYVE and coiled-coil domain containing 1) functions as an autophagy adaptor in directly linking autophagosomes with the microtubule-based kinesin motor, and plays an essential role in the microtubule plus end-directed transport of autophagic vesicles. The specific association of FYCO1 with autophagosomes is mediated by its interaction with Atg8-family proteins decorated on the outer surface of autophagosome. However, the mechanistic basis governing the interaction between FYCO1 and Atg8-family proteins is largely unknown. Here, using biochemical and structural analyses, we demonstrated that FYCO1 contains a unique LC3-interacting region (LIR), which discriminately binds to mammalian Atg8 orthologs and preferentially binds to the MAP1LC3A and MAP1LC3B. In addition to uncovering the detailed molecular mechanism underlying the FYCO1 LIR and MAP1LC3A interaction, the determined FYCO1-LIR-MAP1LC3A complex structure also reveals a unique LIR binding mode for Atg8-family proteins, and demonstrates, first, the functional relevance of adjacent sequences C-terminal to the LIR core motif for binding to Atg8-family proteins. Taken together, our findings not only provide new mechanistic insight into FYCO1-mediated transport of autophagosomes, but also expand our understanding of the interaction modes between LIR motifs and Atg8-family proteins in general.
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MAP1LC3A is a microtubule associated protein that mediates the interaction between microtubules and the cytoskeleton and is a key protein in the autophagy pathway.
“MAP1LC3A (FC = −1.34, p = 0.04) is a microtubule associated protein which mediates the interaction between microtubules and the cytoskeleton [22] and is a key protein in the autophagy pathway.”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [22]
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Self-citationExploiting autophagy and related pathways: pioneering new horizons in cataract therapy
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Molecular bases of the interactions of ATG16L1 with FIP200 and ATG8 family proteins
Gong, X., Zhou, Y., Wang, Y., Tang, Y., Liu, H., Zhou, X., Zhang, Y., Guo, H., Guo, Z., & Pan, L. (2025) · Nature Communications · doi:10.1038/s41467-025-64097-4 · Cited by 7 · see citing works
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FYCO1 regulates autophagy and senescence via PAK1/p21 in cataract
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A proteome-wide biochemical screen defines binding determinants of the core autophagy protein LC3BPreprint
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A proteome-wide biochemical screen defines binding determinants of the core autophagy protein LC3BPreprint
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A proteome-wide biochemical screen defines binding determinants of the core autophagy protein LC3BPreprint
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- Authors
- Cheng, X., Wang, Y., Gong, Y., Li, F., Guo, Y., Hu, S., Liu, J., & Pan, L.
- Affiliations
- State Key Laboratory of Biorganic and Natural Products Chemistry, Shanghai, China
- Chinese Academy of Sciences (CN)
- Corresponding author
- Pan, Lifeng
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-06-24
- Volume
- 12
- Issue
- 8
- Pages
- 1330-1339
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4968224
- OpenAlex
- W2419085352
- Cited by
- 62
- References
- 48
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 15 · 2020: 9 · 2019: 8 · 2018: 2 · 2017: 3 · 2016: 1
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Salt Science Research Foundation (BL19U1)
- National Natural Science Foundation of China (13QA1404300, 31470749, BL19U1)
- Chinese Academy of Sciences
- Recruitment Program of Global Experts
- Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
- National Key Research and Development Program of China (2013CB836900)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- FYCO1, MAP1LC3A, LC3B, Atg8-family proteins, LC3-interacting region, autophagosome transport, kinesin motors, protein-protein interaction, binding mode, crystal structure
- MeSH terms
- Autophagy-Related Protein 8 Family, Autophagy, Chromatography, Gel, DNA-Binding Proteins, HeLa Cells, Humans, Microtubule-Associated Proteins, Microtubules, Magnetic Resonance Spectroscopy, Protein Binding, Recombinant Proteins, Transcription Factors, Kinesins, DNA, Complementary, Amino Acid Motifs
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