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EMBO Rep., 2021 Jun 4;22(6):e51323 | https://doi.org/10.15252/embr.202051323 Phospholipid transfer function of PTPIP51 at mitochondria‐associated ER membranes

Hyun Ku Yeo ^{1 †}, Tae Hyun Park ^{1 2 †}, Hee Yeon Kim ¹, Hyonchol Jang ^{1 3}, Jueun Lee ⁴, Geum-Sook Hwang ^{4 5}, Seong Eon Ryu ², Si Hoon Park ⁶, Hyun Kyu Song ⁶, Hyun Seung Ban ⁷, Hye-Jin Yoon ⁸, Byung Il Lee ^{1 3 *}

¹Research Institute, National Cancer Center, Goyang-si, Korea.

²Department of Bioengineering, Hanyang University, Seoul, Korea.

³Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang-si, Korea.

⁴Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Korea.

⁵Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Korea.

⁶Department of Life Sciences, Korea University, Seoul, Korea.

⁷Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.

⁸Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, Korea.

^†These authors contributed equally
^*Corresponding author: correspondence to Byung Il Lee

Abstract

In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria‐associated ER membranes (MAMs). Ca2⁺ 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.

논문정보

형식Research article
게재일2021년 06월 (BRIC 등록일 2024-05-07)
연구진국내 연구진
분야 생명과학 > 구조생물 및 생물물리학
피인용횟수60회 이상 인용된 논문

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