7DNY

Cryo-EM structure of the human ABCB6 (coproporphyrin III-bound)

Summary for 7DNY

• Entry DOI: 10.2210/pdb7dny/pdb
• EMDB information: 30790
• Descriptor: ATP-binding cassette sub-family B member 6, mitochondrial, CHOLESTEROL HEMISUCCINATE, coproporphyrin III (3 entities in total)
• Functional Keywords: abcb6, heme transporter, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 191036.68

Authors

Kim, S.,Lee, S.S.,Park, J.G.,Kim, J.W.,Kim, S.,Kim, N.J.,Hong, S.,Kang, J.Y.,Jin, M.S. (deposition date: 2020-12-11, release date: 2022-06-22, Last modification date: 2024-06-05)

Primary citation

Kim, S.,Lee, S.S.,Park, J.G.,Kim, J.W.,Ju, S.,Choi, S.H.,Kim, S.,Kim, N.J.,Hong, S.,Kang, J.Y.,Jin, M.S.
Structural Insights into Porphyrin Recognition by the Human ATP-Binding Cassette Transporter ABCB6.
Mol.Cells, 45:575-587, 2022

PubMed Abstract: Human ABCB6 is an ATP-binding cassette transporter that regulates heme biosynthesis by translocating various porphyrins from the cytoplasm into the mitochondria. Here we report the cryo-electron microscopy (cryo-EM) structures of human ABCB6 with its substrates, coproporphyrin III (CPIII) and hemin, at 3.5 and 3.7 Å resolution, respectively. Metalfree porphyrin CPIII binds to ABCB6 within the central cavity, where its propionic acids form hydrogen bonds with the highly conserved Y550. The resulting structure has an overall fold similar to the inward-facing apo structure, but the two nucleotide-binding domains (NBDs) are slightly closer to each other. In contrast, when ABCB6 binds a metal-centered porphyrin hemin in complex with two glutathione molecules (1 hemin: 2 glutathione), the two NBDs end up much closer together, aligning them to bind and hydrolyze ATP more efficiently. In our structures, a glycine-rich and highly flexible "bulge" loop on TM helix 7 undergoes significant conformational changes associated with substrate binding. Our findings suggest that ABCB6 utilizes at least two distinct mechanisms to fine-tune substrate specificity and transport efficiency.

PubMed: 35950458
DOI: 10.14348/molcells.2022.0040

Experimental method

ELECTRON MICROSCOPY (3.4 Å)