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7d7n

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Cryo-EM structure of human ABCB6 transporterCryo-EM structure of human ABCB6 transporter

Structural highlights

7d7n is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:ABCB6, MTABC3, PRP, UMAT (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ABCB6_HUMAN] Ocular coloboma;Dyschromatosis universalis;Colobomatous microphthalmia. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. ABCB6 mutations are involved in familial pseudohyperkalemia, a dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape (PubMed:23180570).[1]

Function

[ABCB6_HUMAN] Binds heme and porphyrins and functions in their ATP-dependent uptake into the mitochondria. Plays a crucial role in heme synthesis.[2] [3]

Publication Abstract from PubMed

Human ATP-binding cassette transporter 6 of subfamily B (ABCB6) is an ABC transporter involved in the translocation toxic metals and anti-cancer drugs. Using cryo-electron microscopy, we determined the molecular structure of full-length ABCB6 in an apo state. The structure of ABCB6 unravels the architecture of a full-length ABCB transporter that harbors two N-terminal transmembrane domains which is indispensable for its ATPase activity in our in vitro assay. A slit-like substrate binding pocket of ABCB6 may accommodate the planar shape of porphyrins, and the existence of a secondary cavity near the mitochondrial intermembrane space side would further facilitate substrate release. Furthermore, the ATPase activity of ABCB6 stimulated with a variety of porphyrin substrates showed different profiles in the presence of glutathione (GSH), suggesting the action of a distinct substrate translocation mechanism depending on the use of GSH as a cofactor.

Cryo-electron microscopy structure of human ABCB6 transporter.,Wang C, Cao C, Wang N, Wang X, Wang X, Zhang XC Protein Sci. 2020 Oct 2. doi: 10.1002/pro.3960. PMID:33007128[4]

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

References

  1. ↑ Andolfo I, Alper SL, Delaunay J, Auriemma C, Russo R, Asci R, Esposito MR, Sharma AK, Shmukler BE, Brugnara C, De Franceschi L, Iolascon A. Missense mutations in the ABCB6 transporter cause dominant familial pseudohyperkalemia. Am J Hematol. 2013 Jan;88(1):66-72. doi: 10.1002/ajh.23357. Epub 2012 Nov 24. PMID:23180570 doi:http://dx.doi.org/10.1002/ajh.23357
  2. ↑ Mitsuhashi N, Miki T, Senbongi H, Yokoi N, Yano H, Miyazaki M, Nakajima N, Iwanaga T, Yokoyama Y, Shibata T, Seino S. MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis. J Biol Chem. 2000 Jun 9;275(23):17536-40. PMID:10837493
  3. ↑ Krishnamurthy PC, Du G, Fukuda Y, Sun D, Sampath J, Mercer KE, Wang J, Sosa-Pineda B, Murti KG, Schuetz JD. Identification of a mammalian mitochondrial porphyrin transporter. Nature. 2006 Oct 5;443(7111):586-9. Epub 2006 Sep 27. PMID:17006453 doi:http://dx.doi.org/10.1038/nature05125
  4. ↑ Wang C, Cao C, Wang N, Wang X, Wang X, Zhang XC. Cryo-electron microscopy structure of human ABCB6 transporter. Protein Sci. 2020 Oct 2. doi: 10.1002/pro.3960. PMID:33007128 doi:http://dx.doi.org/10.1002/pro.3960

7d7n, resolution 5.20Å

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