6i3y

From Proteopedia

(Difference between revisions)

Revision as of 07:51, 10 April 2019

Crystal structure of the human mitochondrial PRELID1K58V-TRIAP1 complex with PS

Structural highlights

6i3y is a 4 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:	PRELID1, PRELI, CGI-106, SBBI12 (HUMAN), TRIAP1, 15E1.1, HSPC132 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PRLD1_HUMAN] Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane. Regulates the mitochondrial apoptotic pathway in primary Th cells. Regulates Th cell differentiation by down-regulating STAT6 thereby reducing IL-4-induced Th2 cell number. May be important for the development of vital and immunocompetent organs.^[1] ^[2] ^[3] [TRIA1_HUMAN] Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane (PubMed:23931759). Likewise, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes (in vitro) and probably functions as a PA transporter across the mitochondrion intermembrane space (in vivo) (PubMed:26071602). Mediates cell survival by inhibiting activation of caspase-9 which prevents induction of apoptosis (PubMed:15735003).^[4] ^[5]

Publication Abstract from PubMed

Conserved lipid transfer proteins of the Ups/PRELI family regulate lipid accumulation in mitochondria by shuttling phospholipids in a lipid-specific manner across the intermembrane space. Here, we combine structural analysis, unbiased genetic approaches in yeast and molecular dynamics simulations to unravel determinants of lipid specificity within the conserved Ups/PRELI family. We present structures of human PRELID1-TRIAP1 and PRELID3b-TRIAP1 complexes, which exert lipid transfer activity for phosphatidic acid and phosphatidylserine, respectively. Reverse yeast genetic screens identify critical amino acid exchanges that broaden and swap their lipid specificities. We find that amino acids involved in head group recognition and the hydrophobicity of flexible loops regulate lipid entry into the binding cavity. Molecular dynamics simulations reveal different membrane orientations of PRELID1 and PRELID3b during the stepwise release of lipids. Our experiments thus define the structural determinants of lipid specificity and the dynamics of lipid interactions by Ups/PRELI proteins.

Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins.,Miliara X, Tatsuta T, Berry JL, Rouse SL, Solak K, Chorev DS, Wu D, Robinson CV, Matthews S, Langer T Nat Commun. 2019 Mar 8;10(1):1130. doi: 10.1038/s41467-019-09089-x. PMID:30850607^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tahvanainen J, Kallonen T, Lahteenmaki H, Heiskanen KM, Westermarck J, Rao KV, Lahesmaa R. PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation. Blood. 2009 Feb 5;113(6):1268-77. doi: 10.1182/blood-2008-07-166553. Epub 2008, Oct 22. PMID:18945965 doi:http://dx.doi.org/10.1182/blood-2008-07-166553
↑ McKeller MR, Herrera-Rodriguez S, Ma W, Ortiz-Quintero B, Rangel R, Cande C, Sims-Mourtada JC, Melnikova V, Kashi C, Phan LM, Chen Z, Huang P, Dunner K Jr, Kroemer G, Singh KK, Martinez-Valdez H. Vital function of PRELI and essential requirement of its LEA motif. Cell Death Dis. 2010;1:e21. doi: 10.1038/cddis.2009.19. PMID:21364629 doi:http://dx.doi.org/10.1038/cddis.2009.19
↑ Potting C, Tatsuta T, Konig T, Haag M, Wai T, Aaltonen MJ, Langer T. TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab. 2013 Aug 6;18(2):287-95. doi: 10.1016/j.cmet.2013.07.008. PMID:23931759 doi:http://dx.doi.org/10.1016/j.cmet.2013.07.008
↑ Park WR, Nakamura Y. p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway. Cancer Res. 2005 Feb 15;65(4):1197-206. PMID:15735003 doi:http://dx.doi.org/65/4/1197
↑ Potting C, Tatsuta T, Konig T, Haag M, Wai T, Aaltonen MJ, Langer T. TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab. 2013 Aug 6;18(2):287-95. doi: 10.1016/j.cmet.2013.07.008. PMID:23931759 doi:http://dx.doi.org/10.1016/j.cmet.2013.07.008
↑ Miliara X, Tatsuta T, Berry JL, Rouse SL, Solak K, Chorev DS, Wu D, Robinson CV, Matthews S, Langer T. Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins. Nat Commun. 2019 Mar 8;10(1):1130. doi: 10.1038/s41467-019-09089-x. PMID:30850607 doi:http://dx.doi.org/10.1038/s41467-019-09089-x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6i3y"

@@ Line 3: / Line 3: @@
 <StructureSection load='6i3y' size='340' side='right'caption='[[6i3y]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6i3y]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I3Y FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6i3y]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I3Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I3Y FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRELID1, PRELI, CGI-106, SBBI12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TRIAP1, 15E1.1, HSPC132 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i3y OCA], [http://pdbe.org/6i3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i3y RCSB], [http://www.ebi.ac.uk/pdbsum/6i3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i3y ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Berry, J L]]

6i3y

From Proteopedia

Revision as of 07:51, 10 April 2019

Crystal structure of the human mitochondrial PRELID1K58V-TRIAP1 complex with PS

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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