24vd: Difference between revisions

Latest revision as of 12:41, 1 July 2026

Structure of substrate-bound ABCD4-LMBD1 complex

Structural highlights

24vd is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.83Å
Ligands:	ATP, CLR, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ABCD4_HUMAN Methylmalonic acidemia with homocystinuria, type cblJ. The disease is caused by mutations affecting the gene represented in this entry.

Function

ABCD4_HUMAN May be involved in intracellular processing of vitamin B12 (cobalamin). Could play a role in the lysosomal release of vitamin B12 into the cytoplasm.^[1]

Publication Abstract from PubMed

Correct trafficking of lysosomal transporters is essential for intracellular homeostasis. While most lysosomal membrane proteins are directed to the lysosome via sorting motifs, the cobalamin exporter ABCD4 is distinct, instead relying on LMBD1 as a dedicated chaperone for its trafficking. Dysfunction of either protein causes inherited cobalamin metabolism disorders. Despite its physiological significance, the molecular mechanism underlying this chaperone-dependent trafficking remains unclear. Here, we report the cryo-EM structures of ABCD4 complex with LMBD1 in the lumen-open, substrate-bound and cytosol-open states. LMBD1 contains nine transmembrane-helices (TMs) and a cytosolic domain, both of which engage ABCD4. Cell imaging shows that disruption of these interactions impairs the trafficking of ABCD4 to lysosomes. Structural and biochemical analyses provide insights into cobalamin recognition and reveal conformational states associated with the proposed cobalamin transport cycle. These findings provide molecular insights into cobalamin metabolism and illustrate a chaperone-assisted mechanism that supports proper trafficking of a lysosomal transporter.

Structural basis for LMBD1-dependent trafficking and cobalamin export of ABCD4.,Liu Q, Li X, Wu Y, Zheng K, Zhou M, Long T Nat Commun. 2026 Jun 16. doi: 10.1038/s41467-026-74552-5. PMID:42303638^[2]

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

References

↑ Coelho D, Kim JC, Miousse IR, Fung S, du Moulin M, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nurnberg P, Thiele H, Robenek H, Hohne W, Longo N, Pasquali M, Mengel E, Watkins D, Shoubridge EA, Majewski J, Rosenblatt DS, Fowler B, Rutsch F, Baumgartner MR. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet. 2012 Oct;44(10):1152-5. doi: 10.1038/ng.2386. Epub 2012 Aug 26. PMID:22922874 doi:https://dx.doi.org/10.1038/ng.2386
↑ Liu Q, Li X, Wu Y, Zheng K, Zhou M, Long T. Structural basis for LMBD1-dependent trafficking and cobalamin export of ABCD4. Nat Commun. 2026 Jun 16. PMID:42303638 doi:10.1038/s41467-026-74552-5

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Coelho D, Kim JC, Miousse IR, Fung S, du Moulin M, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nurnberg P, Thiele H, Robenek H, Hohne W, Longo N, Pasquali M, Mengel E, Watkins D, Shoubridge EA, Majewski J, Rosenblatt DS, Fowler B, Rutsch F, Baumgartner MR. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet. 2012 Oct;44(10):1152-5. doi: 10.1038/ng.2386. Epub 2012 Aug 26. PMID:22922874 doi:https://dx.doi.org/10.1038/ng.2386

[2] Liu Q, Li X, Wu Y, Zheng K, Zhou M, Long T. Structural basis for LMBD1-dependent trafficking and cobalamin export of ABCD4. Nat Commun. 2026 Jun 16. PMID:42303638 doi:10.1038/s41467-026-74552-5

[1]

[2]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 24vd is ON HOLD  until Paper Publication
+==Structure of substrate-bound ABCD4-LMBD1 complex==
+<StructureSection load='24vd' size='340' side='right'caption='[[24vd]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[24vd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=24VD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=24VD FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.83&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=24vd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=24vd OCA], [https://pdbe.org/24vd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=24vd RCSB], [https://www.ebi.ac.uk/pdbsum/24vd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=24vd ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ABCD4_HUMAN ABCD4_HUMAN] Methylmalonic acidemia with homocystinuria, type cblJ. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/ABCD4_HUMAN ABCD4_HUMAN] May be involved in intracellular processing of vitamin B12 (cobalamin). Could play a role in the lysosomal release of vitamin B12 into the cytoplasm.<ref>PMID:22922874</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Correct trafficking of lysosomal transporters is essential for intracellular homeostasis. While most lysosomal membrane proteins are directed to the lysosome via sorting motifs, the cobalamin exporter ABCD4 is distinct, instead relying on LMBD1 as a dedicated chaperone for its trafficking. Dysfunction of either protein causes inherited cobalamin metabolism disorders. Despite its physiological significance, the molecular mechanism underlying this chaperone-dependent trafficking remains unclear. Here, we report the cryo-EM structures of ABCD4 complex with LMBD1 in the lumen-open, substrate-bound and cytosol-open states. LMBD1 contains nine transmembrane-helices (TMs) and a cytosolic domain, both of which engage ABCD4. Cell imaging shows that disruption of these interactions impairs the trafficking of ABCD4 to lysosomes. Structural and biochemical analyses provide insights into cobalamin recognition and reveal conformational states associated with the proposed cobalamin transport cycle. These findings provide molecular insights into cobalamin metabolism and illustrate a chaperone-assisted mechanism that supports proper trafficking of a lysosomal transporter.
-Authors:
+Structural basis for LMBD1-dependent trafficking and cobalamin export of ABCD4.,Liu Q, Li X, Wu Y, Zheng K, Zhou M, Long T Nat Commun. 2026 Jun 16. doi: 10.1038/s41467-026-74552-5. PMID:42303638<ref>PMID:42303638</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 24vd" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Liu Q]]
+[[Category: Long T]]

24vd: Difference between revisions

Latest revision as of 12:41, 1 July 2026

Structure of substrate-bound ABCD4-LMBD1 complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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