The lysosomal protein ABCD4 can transport vitamin B12 across liposomal membranes in vitro

Kitai, Katsuki; Kawaguchi, Kosuke; Tomohiro, Takenori; Morita, Masashi; So, Takanori; Imanaka, Tsuneo

doi:10.1016/j.jbc.2021.100654

Cited by 21 publications

(41 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The LMBD1 protein, encoded by the LMBRD1 gene, was suggested to function as a vitamin B12 (cobalamin) transporter, exporting vitamin B12 from the lysosomes into the cytoplasm [ 147 ]. However, it was later shown that LMBD1 actually interacts with ABCD4 and assists in its lysosomal trafficking [ 148 ], and that ABCD4 transports vitamin B12 even in the absence of LMBD1 [ 149 ]. Therefore, it is likely that LMBD1 itself is not a vitamin B12 transporter.…”

Section: Discussionmentioning

confidence: 99%

Systematic in silico discovery of novel solute carrier-like proteins from proteomes

Gyimesi

Hediger

2022

PLoS ONE

View full text Add to dashboard Cite

Solute carrier (SLC) proteins represent the largest superfamily of transmembrane transporters. While many of them play key biological roles, their systematic analysis has been hampered by their functional and structural heterogeneity. Based on available nomenclature systems, we hypothesized that many as yet unidentified SLC transporters exist in the human genome, which await further systematic analysis. Here, we present criteria for defining “SLC-likeness” to curate a set of “SLC-like” protein families from the Transporter Classification Database (TCDB) and Protein families (Pfam) databases. Computational sequence similarity searches surprisingly identified ~120 more proteins in human with potential SLC-like properties compared to previous annotations. Interestingly, several of these have documented transport activity in the scientific literature. To complete the overview of the “SLC-ome”, we present an algorithm to classify SLC-like proteins into protein families, investigating their known functions and evolutionary relationships to similar proteins from 6 other clinically relevant experimental organisms, and pinpoint structural orphans. We envision that our work will serve as a stepping stone for future studies of the biological function and the identification of the natural substrates of the many under-explored SLC transporters, as well as for the development of new therapeutic applications, including strategies for personalized medicine and drug delivery.

show abstract

Section: Discussionmentioning

confidence: 99%

Systematic in silico discovery of novel solute carrier-like proteins from proteomes

Gyimesi

Hediger

2022

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Recently, we demonstrated that ABCD4 possesses cobalamin transport activity across the liposomal membrane in vitro. 25) ABCD4 had been purified according to the same procedure as ABCD1. We prepared ABCD4-liposomes including cobalamin and incubated them with the addition of ATP outside of the liposomes, and then quantified cobalamin release from the liposomes by reverse-phase HPLC.…”

Section: The Transport Mechanism Of Abcd1 and Abcd4mentioning

confidence: 99%

“…24) Recently, we demonstrated that ABCD4 reconstituted into liposomes is capable of transporting cobalamin from the inside to the outside of liposomes in an ATPase activity-dependent manner. 25) In addition, it is predicted that ABCD4 possesses the topological feature where the COOH-terminal half, including the NBD, is exposed to the cytosol. 26) These strongly suggest that ABCD4 is able to transport cobalamin from the inside of lysosomes to the cytosol; that is, ABCD4 functions as an importer.…”

Section: Introductionmentioning

confidence: 99%

Substrate Specificity and the Direction of Transport in the ABC Transporters ABCD1–3 and ABCD4

Kawaguchi

Imanaka

2022

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

The ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and exist in almost all living organisms from eubacteria to mammals. They transport diverse substrates across membranes utilizing the energy of ATP hydrolysis as a driving force and play an essential role in cellular homeostasis. In humans, four ABC transporters classified as subfamily D have been identified. ABCD1-3 are localized to peroxisomal membranes and involved in the transport of various acyl-CoAs from the cytosol to the peroxisomal lumen. ABCD4 functions on the lysosomal membranes and transports vitamin B 12 (cobalamin) from lysosomes into the cytosol. The mutation of genes encoding ABCD1, ABCD3, and ABCD4 are responsible for genetic diseases called X-linked adrenoleukodystrophy, congenital bile acid synthesis defect 5, and cobalamin deficiency, respectively. In this review, we summarize the targeting mechanism and physiological functions of the ABCD transporters and discuss insights that have been obtained on the transport mechanism based on disease-causing mutations and cryo-electron microscopy (EM) structural studies.

show abstract

“…The LMBD1 protein, encoded by the LMBRD1 gene, was suggested to function as a vitamin B12 (cobalamin) transporter, exporting vitamin B12 from the lysosomes into the cytoplasm [126]. However, it was later shown that LMBD1 actually interacts with ABCD4 and assists in its lysosomal trafficking [127], and that ABCD4 transports vitamin B12 even in the absence of LMBD1 [128]. Therefore, it is likely that LMBD1 itself is not a vitamin B12 transporter.…”

Section: Putative Transportersmentioning

confidence: 99%

“…and that ABCD4 transports vitamin B12 even in the absence of LMBD1 [149]. Therefore, it is likely that LMBD1 itself is not a vitamin B12 transporter.…”

Section: Putative Transportersmentioning

confidence: 99%

Systematic in silico discovery of novel solute carrier-like proteins from proteomes

Gyimesi

Hediger

2021

Preprint

View full text Add to dashboard Cite

Solute carrier (SLC) proteins represent the largest superfamily of transmembrane transporters, the systematic analysis of which is hampered by their functional and structural heterogeneity, despite their biological importance. Based on available nomenclature systems, we suspected that many as yet unidentified SLC transporters exist in the human genome. Here, we present criteria for defining “SLC-likeness” and apply them to curate a set of “SLC-like” protein families from the Transporter Classification Database (TCDB) and Protein families (Pfam) databases. Computational sequence similarity searches then surprisingly yielded ∼130 more proteins in human with SLC-like properties, compared to previous annotations. Several of these novel putative SLC transporter proteins actually have documented transport activity in the scientific literature. We complete our overview of the SLC-ome by presenting an algorithm to classify SLC-like proteins into protein families, investigating their known functions and evolutionary relationships to similar proteins from 6 other clinically relevant experimental organisms, and pinpointing structural orphans. We envision that our work will serve as a stepping stone for future studies of the biological function and the identification of the natural substrates of the many under-explored SLC transporters, as well as the development of new therapeutic applications, including strategies for personalized medicine and drug delivery.

show abstract

The lysosomal protein ABCD4 can transport vitamin B12 across liposomal membranes in vitro

Cited by 21 publications

References 36 publications

Systematic in silico discovery of novel solute carrier-like proteins from proteomes

Systematic in silico discovery of novel solute carrier-like proteins from proteomes

Substrate Specificity and the Direction of Transport in the ABC Transporters ABCD1–3 and ABCD4

Systematic in silico discovery of novel solute carrier-like proteins from proteomes

Contact Info

Product

Resources

About