Structures of human organellar SPFH protein complexes.

Area of Science:

• Biochemistry
• Structural Biology
• Cell Biology

Background:

• Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) proteins are conserved across life and found in various organelles.
• SPFH proteins assemble into ring-shaped structures at cellular membranes, involved in membrane organization and protein quality control.
• The precise architectures of SPFH complexes are not fully understood.

Purpose of the Study:

• To determine the high-resolution structures of human organellar SPFH complexes.
• To elucidate the assembly principles and stoichiometries of these complexes.
• To understand the common organizational strategies of SPFH proteins.

Main Methods:

• Single-particle cryo-electron microscopy (cryo-EM) was employed.
• Structures of the Erlin1/2 complex (ER-resident) and the Prohibitin (PHB1/2) complex (mitochondrial) were determined.
• Analysis of protein-protein interactions and conformational heterogeneity was performed.

Main Results:

• The Erlin1/2 complex consists of 13 heterodimers of Erlin1 and Erlin2.
• The PHB1/2 complex comprises 11 heterodimers of PHB1 and PHB2.
• Key interactions defining complex architecture and conformational variations in the PHB1/2 complex were identified.

Conclusions:

• Distinct stoichiometries and architectures characterize human organellar SPFH complexes.
• Common principles govern the organization of SPFH protein assemblies.
• These findings provide insights into the structure-function relationships of SPFH proteins in cellular membranes.