Structure of full-length ERGIC-53 in complex with MCFD2 for cargo transport
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Abstract
ERGIC-53 transports certain subsets of newly synthesized secretory proteins and membrane proteins from the endoplasmic reticulum to the Golgi apparatus. Despite numerous structural and functional studies since its identification, the overall architecture and mechanism of action of ERGIC-53 remain unclear. Here we present cryo-EM structures of full-length ERGIC-53 in complex with its functional partner MCFD2. These structures reveal that ERGIC-53 exists as a homotetramer, not a homohexamer as previously suggested, and comprises a four-leaf clover-like head and a long stalk composed of three sets of four-helix coiled-coil followed by a transmembrane domain. 3D variability analysis visualizes the flexible motion of the long stalk and local plasticity of the head region. Notably, MCFD2 is shown to possess a Zn 2+ -binding site in its N-terminal lid, which appears to modulate cargo binding. Altogether, distinct mechanisms of cargo capture and release by ERGIC- 53 via the stalk bending and metal binding are proposed.
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Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex
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- Authors
- Watanabe, S., Kise, Y., Yonezawa, K., Inoue, M., Shimizu, N., Nureki, O., & Inaba, K.
- Affiliations
- Tohoku University (JP)
- The University of Tokyo (JP)
- High Energy Accelerator Research Organization (JP)
- Kyushu University (JP)
- Corresponding author
- Watanabe, Satoshi
- Inaba, Kenji
- Venue
- Nature Communications
- Published
- 2024-03-16
- Volume
- 15
- Issue
- 1
- Pages
- 2404-2404
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10944485
- OpenAlex
- W4392878896
- Cited by
- 12
- References
- 3
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 1
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Naito Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Ministry of Education, Culture, Sports, Science and Technology (JP18K06075,JP21H05253, JP23K18193, JP21H05253)
- Japan Agency for Medical Research and Development (JP22gm6410026, 21gm1410006h0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- ERGIC-53, MCFD2, homotetramer, freight transport, secretory protein transport, Golgi apparatus, endoplasmic reticulum, transmembrane domain, cargo binding, cargo release, protein structure
- MeSH terms
- Binding Sites, Golgi Apparatus, Membrane Proteins, Protein Binding, Vesicular Transport Proteins, Mannose-Binding Lectins
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