7CC7

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

Summary for 7CC7

• Entry DOI: 10.2210/pdb7cc7/pdb
• Descriptor: Regulator of microtubule dynamics protein 3, PARA-TOLUENE SULFONATE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: tpr, ptpip51, mitochondria, endoplasmic reticulum, mam, phopsphplipid, lipid transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 27402.99

Authors

Lee, B.I.,Park, T.H.,Yeo, H.K. (deposition date: 2020-06-16, release date: 2021-01-20, Last modification date: 2024-03-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.45 Å)