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Structure paper

TitleStructure of full-length ERGIC-53 in complex with MCFD2 for cargo transport.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 2404, Year 2024
Publish dateMar 16, 2024
AuthorsSatoshi Watanabe / Yoshiaki Kise / Kento Yonezawa / Mariko Inoue / Nobutaka Shimizu / Osamu Nureki / Kenji Inaba /
PubMed AbstractERGIC-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 ...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-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.
External linksNat Commun / PubMed:38493152 / PubMed Central
MethodsEM (single particle)
Resolution2.53 - 6.76 Å
Structure data

36467

8jp4

EMDB-36467, PDB-8jp4:
Cryo-EM structure of the head region of full-length ERGIC-53 with MCFD2 (form A)
Method: EM (single particle) / Resolution: 2.53 Å

36468

8jp5

EMDB-36468, PDB-8jp5:
Cryo-EM structures of the head region of full-length ERGIC-53 with MCFD2 (form B)
Method: EM (single particle) / Resolution: 2.59 Å

36469

8jp6

EMDB-36469, PDB-8jp6:
Cryo-EM structures of the head region of full-length ERGIC-53 with MCFD2 (Substate A)
Method: EM (single particle) / Resolution: 3.29 Å

36470

8jp7

EMDB-36470, PDB-8jp7:
Cryo-EM structure of the head region of full-length ERGIC-53 with MCFD2 (Substate B)
Method: EM (single particle) / Resolution: 3.51 Å

36471

8jp8

EMDB-36471, PDB-8jp8:
Cryo-EM structure of the head region of full-length ERGIC-53 with MCFD2 (Substate C)
Method: EM (single particle) / Resolution: 3.39 Å

36472

8jp9

EMDB-36472, PDB-8jp9:
Cryo-EM structure of the head region of full-length ERGIC-53 with MCFD2 (Substate D)
Method: EM (single particle) / Resolution: 3.37 Å

36479

8jpg

EMDB-36479, PDB-8jpg:
Cryo-EM structure of full-length ERGIC-53 with MCFD2
Method: EM (single particle) / Resolution: 6.76 Å

EMDB-36482: cryoEM structure of ERGIC-53 deltaH34 mutant with MCFD2
Method: EM (single particle) / Resolution: 3.78 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsPROTEIN TRANSPORT / cargo receptor / calcium / zinc

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