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TitleMethionine aminopeptidase 2 and its autoproteolysis product have different binding sites on the ribosome.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 716, Year 2024
Publish dateJan 24, 2024
AuthorsMarius A Klein / Klemens Wild / Miglė Kišonaitė / Irmgard Sinning /
PubMed AbstractExcision of the initiator methionine is among the first co-translational processes that occur at the ribosome. While this crucial step in protein maturation is executed by two types of methionine ...Excision of the initiator methionine is among the first co-translational processes that occur at the ribosome. While this crucial step in protein maturation is executed by two types of methionine aminopeptidases in eukaryotes (MAP1 and MAP2), additional roles in disease and translational regulation have drawn more attention to MAP2. Here, we report several cryo-EM structures of human and fungal MAP2 at the 80S ribosome. Irrespective of nascent chains, MAP2 can occupy the tunnel exit. On nascent chain displaying ribosomes, the MAP2-80S interaction is highly dynamic and the MAP2-specific N-terminal extension engages in stabilizing interactions with the long rRNA expansion segment ES27L. Loss of this extension by autoproteolytic cleavage impedes interactions at the tunnel, while promoting MAP2 to enter the ribosomal A-site, where it engages with crucial functional centers of translation. These findings reveal that proteolytic remodeling of MAP2 severely affects ribosome binding, and set the stage for targeted functional studies.
External linksNat Commun / PubMed:38267453 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.3 - 3.1 Å
Structure data

EMDB-17002, PDB-8ony:
Human Methionine Aminopeptidase 2 at the 80S ribosome
Method: EM (single particle) / Resolution: 2.92 Å

EMDB-17003, PDB-8onz:
Chaetomium thermophilum Methionine Aminopeptidase 2 at the 80S ribosome
Method: EM (single particle) / Resolution: 2.94 Å

EMDB-17004, PDB-8oo0:
Chaetomium thermophilum Methionine Aminopeptidase 2 autoproteolysis product at the 80S ribosome
Method: EM (single particle) / Resolution: 3.1 Å

PDB-8onx:
High resolution structure of Chaetomium thermophilum MAP2
Method: X-RAY DIFFRACTION / Resolution: 1.3 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-CO:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • thermochaetoides thermophila (fungus)
  • thermochaetoides thermophila dsm 1495 (fungus)
KeywordsMETAL BINDING PROTEIN / Ribosome Associated Factor / Protease / Tunnel exit / Protein Maturation / Proteostasis / NME / p67 / MAP / MetAP / MAP2 / MetAP2 / ES27L / PTE / A-site / Factor binding site / Decoding center / p26 / Autoproteolysis

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