Crystal structure of Fis1 and Bap31 provides information on protein-protein interactions at mitochondria-associated ER membranes

TL;DR

This study reveals the crystal structure of Fis1 and Bap31, shedding light on how these proteins interact at ER-mitochondria contact sites.

Contribution

The paper presents novel crystal structures of Fis1 and its complex with Bap31, offering new structural insights into ER-mitochondria interactions.

Findings

Fis1 exists in two distinct conformations, one resembling monomeric yeast Fis1 with an autoinhibitory 'Fis1 arm'.

Bap31_vDED interacts with the convex surface of Fis1’s TPR domain, forming a weak but unique interface.

The structures provide insight into how MAM-associated proteins mediate organelle tethering and signaling.

Abstract

In eukaryotic cells, mitochondria and the endoplasmic reticulum (ER) form close contacts at mitochondria-associated ER membranes (MAMs), which are involved in diverse cellular processes. The outer mitochondrial membrane protein Fis1, known for its role in mitochondrial fission, has been reported to interact with the ER-resident protein Bap31. Here, we present crystal structures of the cytosolic domain of human Fis1 in two distinct conformations, along with a co-crystal structure of Fis1 bound to the C-terminal region of the Bap31_vDED domain. One Fis1 structure resembles monomeric yeast Fis1 and features a characteristic N-terminal “Fis1 arm” conformation, which may indicate an autoinhibitory function. In the co-complex, the Bap31_vDED region engages the convex surface of Fis1’s tetratricopeptide repeat (TPR) domain. These findings provide structural insight into the interaction between Fis1 and Bap31 at ER–mitochondria contact sites.

Structural analysis of Fis1-Bap31 interaction reveals a weak but unique interface between 2 proteins, illuminating how MAM-associated proteins mediate organelle tethering and signaling at ER-mitochondria contact sites.

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