| Structural highlights
7cc7 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | RMDN3, FAM82A2, FAM82C, PTPIP51, hucep-10, UNQ3122/PRO10274 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RMD3_HUMAN] Involved in cellular calcium homeostasis regulation. May participate in differentiation and apoptosis of keratinocytes. Overexpression induces apoptosis.[1] [2]
Publication Abstract from PubMed
In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria-associated ER membranes (MAMs). Ca(2+) 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.
Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes.,Yeo HK, Park TH, Kim HY, Jang H, Lee J, Hwang GS, Ryu SE, Park SH, Song HK, Ban HS, Yoon HJ, Lee BI EMBO Rep. 2021 May 2:e51323. doi: 10.15252/embr.202051323. PMID:33938112[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lv BF, Yu CF, Chen YY, Lu Y, Guo JH, Song QS, Ma DL, Shi TP, Wang L. Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis. Apoptosis. 2006 Sep;11(9):1489-501. doi: 10.1007/s10495-006-8882-9. PMID:16820967 doi:http://dx.doi.org/10.1007/s10495-006-8882-9
- ↑ De Vos KJ, Morotz GM, Stoica R, Tudor EL, Lau KF, Ackerley S, Warley A, Shaw CE, Miller CC. VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis. Hum Mol Genet. 2012 Mar 15;21(6):1299-311. doi: 10.1093/hmg/ddr559. Epub 2011 Nov, 30. PMID:22131369 doi:http://dx.doi.org/10.1093/hmg/ddr559
- ↑ Yeo HK, Park TH, Kim HY, Jang H, Lee J, Hwang GS, Ryu SE, Park SH, Song HK, Ban HS, Yoon HJ, Lee BI. Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes. EMBO Rep. 2021 May 2:e51323. doi: 10.15252/embr.202051323. PMID:33938112 doi:http://dx.doi.org/10.15252/embr.202051323
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