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2rr3

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Revision as of 12:25, 23 March 2022

Solution structure of the complex between human VAP-A MSP domain and human OSBP FFAT motif

Structural highlights

2rr3 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[VAPA_HUMAN] May play a role in vesicle trafficking.^[1] ^[2] [OSBP1_HUMAN] Binds cholesterol and a range of oxysterols. Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylate ERK1/2, whereas 25-hydroxycholesterol causes its disassembly. Regulates cholesterol efflux by decreasing ABCA1 stability.^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Oxysterol-binding protein (OSBP), a cytosolic receptor of cholesterol and oxysterols, is recruited to the endoplasmic reticulum by binding to the cytoplasmic major sperm protein (MSP) domain of integral endoplasmic reticulum protein VAMP-associated protein-A (VAP-A), a process essential for the stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. To delineate the interaction mechanism between VAP-A and OSBP, we determined the complex structure between the VAP-A MSP domain (VAP-A(MSP)) and the OSBP fragment containing a VAP-A binding motif FFAT (OSBP(F)) by NMR. This solution structure explained that five of six conserved residues in the FFAT motif are required for the stable complex formation, and three of five, including three critical intermolecular electrostatic interactions, were not explained before. By combining NMR relaxation and titration, isothermal titration calorimetry, and mutagenesis experiments with structural information, we further elucidated the detailed roles of the FFAT motif and underlying motions of VAP-A(MSP), OSBP(F), and the complex. Our results show that OSBP(F) is disordered in the free state, and VAP-A(MSP) and OSBP(F) form a final complex by means of intermediates, where electrostatic interactions through acidic residues, including an acid patch preceding the FFAT motif, probably play a collective role. Additionally, we report that the mutation that causes the familial motor neuron disease decreases the stability of the MSP domain.

Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies.,Furuita K, Jee J, Fukada H, Mishima M, Kojima C J Biol Chem. 2010 Apr 23;285(17):12961-70. Epub 2010 Feb 23. PMID:20178991^[5]

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

References

↑ Weir ML, Xie H, Klip A, Trimble WS. VAP-A binds promiscuously to both v- and tSNAREs. Biochem Biophys Res Commun. 2001 Aug 24;286(3):616-21. PMID:11511104 doi:http://dx.doi.org/10.1006/bbrc.2001.5437
↑ Saita S, Shirane M, Natume T, Iemura S, Nakayama KI. Promotion of neurite extension by protrudin requires its interaction with vesicle-associated membrane protein-associated protein. J Biol Chem. 2009 May 15;284(20):13766-77. doi: 10.1074/jbc.M807938200. Epub 2009, Mar 16. PMID:19289470 doi:10.1074/jbc.M807938200
↑ Wang PY, Weng J, Anderson RG. OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science. 2005 Mar 4;307(5714):1472-6. PMID:15746430 doi:http://dx.doi.org/307/5714/1472
↑ Bowden K, Ridgway ND. OSBP negatively regulates ABCA1 protein stability. J Biol Chem. 2008 Jun 27;283(26):18210-7. Epub 2008 May 1. PMID:18450749 doi:http://dx.doi.org/M800918200
↑ Furuita K, Jee J, Fukada H, Mishima M, Kojima C. Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies. J Biol Chem. 2010 Apr 23;285(17):12961-70. Epub 2010 Feb 23. PMID:20178991 doi:10.1074/jbc.M109.082602

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rr3"

@@ Line 3: / Line 3: @@
 <StructureSection load='2rr3' size='340' side='right'caption='[[2rr3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2rr3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RR3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2RR3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2rr3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RR3 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2rr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rr3 OCA], [http://pdbe.org/2rr3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rr3 RCSB], [http://www.ebi.ac.uk/pdbsum/2rr3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rr3 ProSAT]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rr3 OCA], [https://pdbe.org/2rr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rr3 RCSB], [https://www.ebi.ac.uk/pdbsum/2rr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rr3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/VAPA_HUMAN VAPA_HUMAN]] May play a role in vesicle trafficking.<ref>PMID:11511104</ref> <ref>PMID:19289470</ref>  [[http://www.uniprot.org/uniprot/OSBP1_HUMAN OSBP1_HUMAN]] Binds cholesterol and a range of oxysterols. Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylate ERK1/2, whereas 25-hydroxycholesterol causes its disassembly. Regulates cholesterol efflux by decreasing ABCA1 stability.<ref>PMID:15746430</ref> <ref>PMID:18450749</ref>
+[[https://www.uniprot.org/uniprot/VAPA_HUMAN VAPA_HUMAN]] May play a role in vesicle trafficking.<ref>PMID:11511104</ref> <ref>PMID:19289470</ref>  [[https://www.uniprot.org/uniprot/OSBP1_HUMAN OSBP1_HUMAN]] Binds cholesterol and a range of oxysterols. Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylate ERK1/2, whereas 25-hydroxycholesterol causes its disassembly. Regulates cholesterol efflux by decreasing ABCA1 stability.<ref>PMID:15746430</ref> <ref>PMID:18450749</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

2rr3

From Proteopedia

Revision as of 12:25, 23 March 2022

Solution structure of the complex between human VAP-A MSP domain and human OSBP FFAT motif

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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