Cryo-EM structure of AMP-PNP-bound human mitochondrial ATP-binding cassette transporter ABCB7

• Published in: Journal of structural biology 2022-03, Vol.214 (1), p.107832-107832, Article 107832
• Main Authors: Yan, Qinqin, Shen, Yuequan, Yang, Xue
• Format: Article
• Language: English
• Subjects: ABC transporter; AMP-PNP; Cryo-EM; Human ABCB7
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1016/j.jsb.2022.107832

[Display omitted] •The Cryo-EM structure of hABCB7 was solved at 3.3 Å.•AMP-PNP-Mg2+-bound human ABCB7 exhibits an inward-facing open conformation.•The main substrate-binding pocket of human ABCB7 is positively charged.•Four disease-causing missense mutations of human ABCB7 were mapped to the structure. ATP-binding cassette subfamily B member 7 (ABCB7) is localized in the inner membrane of mitochondria, playing a critical role in iron metabolism. Here, we determined the structure of the nonhydrolyzable ATP analog adenosine-5′-(β-γ-imido) triphosphate (AMP-PNP) bound human ABCB7 at 3.3 Å by single-particle electron cryo-microscopy (cryo-EM). The AMP-PNP-bound human ABCB7 shows an inverted V-shaped homodimeric architecture with an inward-facing open conformation. One AMP-PNP molecule and Mg2+ were identified in each nucleotide-binding domain (NBD) of the hABCB7 monomer. Moreover, four disease-causing missense mutations of human ABCB7 have been mapped to the structure, creating a hotspot map for X-linked sideroblastic anemia and ataxia disease. Our results provide a structural basis for further understanding the transport mechanism of the mitochondrial ABC transporter.