7CC7

Tetratricopeptide repeat (TPR) domain of protein tyrosine phosphatase-interacting protein 51 (PTPIP51)

7CC7 の概要

• エントリーDOI: 10.2210/pdb7cc7/pdb
• 分子名称: Regulator of microtubule dynamics protein 3, PARA-TOLUENE SULFONATE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: tpr, ptpip51, mitochondria, endoplasmic reticulum, mam, phopsphplipid, lipid transport
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27402.99

構造登録者

Lee, B.I.,Park, T.H.,Yeo, H.K. (登録日: 2020-06-16, 公開日: 2021-01-20, 最終更新日: 2024-03-27)

主引用文献

Yeo, H.K.,Park, T.H.,Kim, H.Y.,Jang, H.,Lee, J.,Hwang, G.S.,Ryu, S.E.,Park, S.H.,Song, H.K.,Ban, H.S.,Yoon, H.J.,Lee, B.I.
Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes.
Embo Rep., 22:e51323-e51323, 2021

PubMed Abstract: In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria-associated ER membranes (MAMs). Ca ion and phospholipid transfer occurs at MAMs to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified. Here, we determine the crystal structure of the tetratricopeptide repeat domain of PTPIP51 (PTPIP51_TPR), a mitochondrial protein that interacts with the ER-anchored VAPB protein at MAMs. The structure of PTPIP51_TPR shows an archetypal TPR fold, and an electron density map corresponding to an unidentified lipid-like molecule probably derived from the protein expression host is found in the structure. We reveal functions of PTPIP51 in phospholipid binding/transfer, particularly of phosphatidic acid, in vitro. Depletion of PTPIP51 in cells reduces the mitochondrial cardiolipin level. Additionally, we confirm that the PTPIP51-VAPB interaction is mediated by the FFAT-like motif of PTPIP51 and the MSP domain of VAPB. Our findings suggest that PTPIP51 is a phospholipid transfer protein with a MAM-tethering function.

PubMed: 33938112
DOI: 10.15252/embr.202051323

実験手法

X-RAY DIFFRACTION (1.45 Å)