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Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB
Protein & Cell ; (12): 448-458, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-982526
Biblioteca responsável: WPRO
ABSTRACT
The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Assuntos

Texto completo: Disponível Contexto em Saúde: Doenças Negligenciadas Problema de saúde: Doenças Negligenciadas / Tuberculose Base de dados: WPRIM (Pacífico Ocidental) Assunto principal: Trifosfato de Adenosina / Sideróforos / Transportadores de Cassetes de Ligação de ATP / Microscopia Crioeletrônica / Ferro / Mycobacterium tuberculosis Idioma: Inglês Revista: Protein & Cell Ano de publicação: 2023 Tipo de documento: Artigo
Texto completo: Disponível Contexto em Saúde: Doenças Negligenciadas Problema de saúde: Doenças Negligenciadas / Tuberculose Base de dados: WPRIM (Pacífico Ocidental) Assunto principal: Trifosfato de Adenosina / Sideróforos / Transportadores de Cassetes de Ligação de ATP / Microscopia Crioeletrônica / Ferro / Mycobacterium tuberculosis Idioma: Inglês Revista: Protein & Cell Ano de publicação: 2023 Tipo de documento: Artigo
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