7m1q

From Proteopedia

(Difference between revisions)

Revision as of 20:15, 20 October 2021

Human ABCA4 structure in complex with N-ret-PE

Structural highlights

7m1q 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:	ABCA4, ABCR (HUMAN)
Activity:	P-type phospholipid transporter, with EC number 7.6.2.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ABCA4_HUMAN] Cone rod dystrophy;NON RARE IN EUROPE: Age-related macular degeneration;Stargardt disease;Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

[ABCA4_HUMAN] Catalyzes the translocation of specific phospholipids from the extracellular/lumenal to the cytoplasmic leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylethanolamine (PubMed:24097981). In the visual cycle, acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans-retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. May play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery.^[1] ^[2]

Publication Abstract from PubMed

ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor membranes. Loss-of-function mutations cause Stargardt disease (STGD1), a macular dystrophy associated with severe vision loss. To define the mechanisms underlying substrate binding and STGD1, we determine the cryo-EM structure of ABCA4 in its substrate-free and bound states. The two structures are similar and delineate an elongated protein with the two transmembrane domains (TMD) forming an outward facing conformation, extended and twisted exocytoplasmic domains (ECD), and closely opposed nucleotide binding domains. N-Ret-PE is wedged between the two TMDs and a loop from ECD1 within the lumen leaflet consistent with a lateral access mechanism and is stabilized through hydrophobic and ionic interactions with residues from the TMDs and ECDs. Our studies provide a framework for further elucidating the molecular mechanism associated with lipid transport and disease and developing promising disease interventions.

Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease.,Scortecci JF, Molday LL, Curtis SB, Garces FA, Panwar P, Van Petegem F, Molday RS Nat Commun. 2021 Oct 8;12(1):5902. doi: 10.1038/s41467-021-26161-7. PMID:34625547^[3]

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

References

↑ Sun H, Molday RS, Nathans J. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. J Biol Chem. 1999 Mar 19;274(12):8269-81. doi: 10.1074/jbc.274.12.8269. PMID:10075733 doi:http://dx.doi.org/10.1074/jbc.274.12.8269
↑ Quazi F, Molday RS. Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants. J Biol Chem. 2013 Nov 29;288(48):34414-26. doi: 10.1074/jbc.M113.508812. Epub, 2013 Oct 4. PMID:24097981 doi:http://dx.doi.org/10.1074/jbc.M113.508812
↑ Scortecci JF, Molday LL, Curtis SB, Garces FA, Panwar P, Van Petegem F, Molday RS. Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease. Nat Commun. 2021 Oct 8;12(1):5902. doi: 10.1038/s41467-021-26161-7. PMID:34625547 doi:http://dx.doi.org/10.1038/s41467-021-26161-7

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7m1q"

@@ Line 1: / Line 1: @@
 ==Human ABCA4 structure in complex with N-ret-PE==
-<StructureSection load='7m1q' size='340' side='right'caption='[[7m1q]]' scene=''>
+<StructureSection load='7m1q' size='340' side='right'caption='[[7m1q]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M1Q FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7m1q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M1Q FirstGlance]. <br>
-</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=7m1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m1q OCA], [https://pdbe.org/7m1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m1q RCSB], [https://www.ebi.ac.uk/pdbsum/7m1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m1q ProSAT]</span></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=HZL:[(2S)-3-[2-[(E)-[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenylidene]amino]ethoxy-oxidanyl-phosphoryl]oxy-2-[(Z)-octadec-9-enoyl]oxy-propyl]+(Z)-octadec-9-enoate'>HZL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABCA4, ABCR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/P-type_phospholipid_transporter P-type phospholipid transporter], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=7.6.2.1 7.6.2.1] </span></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=7m1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m1q OCA], [https://pdbe.org/7m1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m1q RCSB], [https://www.ebi.ac.uk/pdbsum/7m1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m1q ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[[https://www.uniprot.org/uniprot/ABCA4_HUMAN ABCA4_HUMAN]] Cone rod dystrophy;NON RARE IN EUROPE: Age-related macular degeneration;Stargardt disease;Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  Disease susceptibility is associated with variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[[https://www.uniprot.org/uniprot/ABCA4_HUMAN ABCA4_HUMAN]] Catalyzes the translocation of specific phospholipids from the extracellular/lumenal to the cytoplasmic leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylethanolamine (PubMed:24097981). In the visual cycle, acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans-retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. May play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery.<ref>PMID:10075733</ref> <ref>PMID:24097981</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor membranes. Loss-of-function mutations cause Stargardt disease (STGD1), a macular dystrophy associated with severe vision loss. To define the mechanisms underlying substrate binding and STGD1, we determine the cryo-EM structure of ABCA4 in its substrate-free and bound states. The two structures are similar and delineate an elongated protein with the two transmembrane domains (TMD) forming an outward facing conformation, extended and twisted exocytoplasmic domains (ECD), and closely opposed nucleotide binding domains. N-Ret-PE is wedged between the two TMDs and a loop from ECD1 within the lumen leaflet consistent with a lateral access mechanism and is stabilized through hydrophobic and ionic interactions with residues from the TMDs and ECDs. Our studies provide a framework for further elucidating the molecular mechanism associated with lipid transport and disease and developing promising disease interventions.
+Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease.,Scortecci JF, Molday LL, Curtis SB, Garces FA, Panwar P, Van Petegem F, Molday RS Nat Commun. 2021 Oct 8;12(1):5902. doi: 10.1038/s41467-021-26161-7. PMID:34625547<ref>PMID:34625547</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7m1q" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Molday RS]]
+[[Category: P-type phospholipid transporter]]
-[[Category: Scortecci JF]]
+[[Category: Molday, R S]]
-[[Category: Van Petegem F]]
+[[Category: Petegem, F Van]]
+[[Category: Scortecci, J F]]
+[[Category: Abc transporter]]
+[[Category: Importer]]
+[[Category: Membrane protein]]
+[[Category: Transport protein]]

7m1q

From Proteopedia

Revision as of 20:15, 20 October 2021

Human ABCA4 structure in complex with N-ret-PE

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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