7X14

Crystal structure of phospho-FFAT motif of MIGA2 bound to VAPB

7X14 の概要

• エントリーDOI: 10.2210/pdb7x14/pdb
• 分子名称: Vesicle-associated membrane protein-associated protein B, MIGA2 phospho FFAT motif, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: ffat, vapb, miga2, lipid transport
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15601.51

構造登録者

Kim, H.,Lee, C. (登録日: 2022-02-23, 公開日: 2022-09-14, 最終更新日: 2023-11-29)

主引用文献

Kim, H.,Lee, S.,Jun, Y.,Lee, C.
Structural basis for mitoguardin-2 mediated lipid transport at ER-mitochondrial membrane contact sites.
Nat Commun, 13:3702-3702, 2022

PubMed Abstract: The endoplasmic reticulum (ER)-mitochondria contact site (ERMCS) is crucial for exchanging biological molecules such as phospholipids and Ca ions between these organelles. Mitoguardin-2 (MIGA2), a mitochondrial outer membrane protein, forms the ERMCS in higher eukaryotic cells. Here, we report the crystal structures of the MIGA2 Lipid Droplet (LD) targeting domain and the ER membrane protein VAPB bound to the phosphorylated FFAT motif of MIGA2. These structures reveal that the MIGA2 LD targeting domain has a large internal hydrophobic pocket that accommodates phospholipids and that two phosphorylations of the FFAT motif are required for tight interaction of MIGA2 with VAPB, which enhances the rate of lipid transport. Further biochemical studies show that MIGA2 transports phospholipids between membranes with a strong preference for binding and trafficking phosphatidylserine (PS). These results provide a structural and molecular basis for understanding how MIGA2 mediates the formation of ERMCS and facilitates lipid trafficking at the ERMCS.

PubMed: 35764626
DOI: 10.1038/s41467-022-31462-6

実験手法

X-RAY DIFFRACTION (1.675 Å)