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Structure paper

TitleStructural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.
Journal, issue, pagesScience, Vol. 379, Issue 6637, Page 1117-1123, Year 2023
Publish dateMar 17, 2023
AuthorsJulian F Ehrmann / Daniel B Grabarczyk / Maria Heinke / Luiza Deszcz / Robert Kurzbauer / Otto Hudecz / Alexandra Shulkina / Rebeca Gogova / Anton Meinhart / Gijs A Versteeg / Tim Clausen /
PubMed AbstractInhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally ...Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers.
External linksScience / PubMed:36758105
MethodsEM (single particle)
Resolution3.3 - 7.2 Å
Structure data

15663

8atu

EMDB-15663, PDB-8atu:
Cryo-EM structure of human BIRC6
Method: EM (single particle) / Resolution: 3.3 Å

15668

8atx

EMDB-15668, PDB-8atx:
Cryo-EM structure of human BIRC6 - no substrate
Method: EM (single particle) / Resolution: 7.0 Å

15672

8auk

EMDB-15672: Cryo-EM structure of human BIRC6 in complex with HTRA2
PDB-8auk: Cryo-EM structure of human BIRC6 in complex with HTRA2.
Method: EM (single particle) / Resolution: 6.2 Å

15675

8auw

EMDB-15675: Cryo-EM structure of human BIRC6 in complex with SMAC
PDB-8auw: Cryo-EM structure of human BIRC6 in complex with SMAC.
Method: EM (single particle) / Resolution: 7.2 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsLIGASE / E3 ubiquitin ligase / E2/E3 hybrid / inhibitor of apoptosis protein

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