A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds.

Rempel, S; Gati, C; Nijland, M; Thangaratnarajah, C; Karyolaimos, A; de Gier, J W; Guskov, A; Slotboom, D J

Rempel, S; Gati, C; Nijland, M; Thangaratnarajah, C; Karyolaimos, A; de Gier, J W; Guskov, A; Slotboom, D J.

Afiliación

Rempel S; Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands.
Gati C; Structural Biology and Biophysics, Biozentrum-University of Basel, Basel, Switzerland.
Nijland M; SLAC National Accelerator Laboratory, Menlo Park, CA, USA. cgati@stanford.edu.
Thangaratnarajah C; Department of Structural Biology, School of Medicine, Stanford University, Palo Alto, CA, USA. cgati@stanford.edu.
Karyolaimos A; Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands.
de Gier JW; Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands.
Guskov A; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Slotboom DJ; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.

Nature ; 580(7803): 409-412, 2020 04.

Article en En | MEDLINE | ID: mdl-32296172

RESUMEN

Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis1-3. Although Mtb can synthesize vitamin B12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis2. Mtb does not encode any characterized cobalamin transporter4-6; however, the gene rv1819c was found to be essential for uptake of cobalamin1. This result is difficult to reconcile with the original annotation of Rv1819c as a protein implicated in the transport of antimicrobial peptides such as bleomycin7. In addition, uptake of cobalamin seems inconsistent with the amino acid sequence, which suggests that Rv1819c has a bacterial ATP-binding cassette (ABC)-exporter fold1. Here, we present structures of Rv1819c, which reveal that the protein indeed contains the ABC-exporter fold, as well as a large water-filled cavity of about 7,700 Å3, which enables the protein to transport the unrelated hydrophilic compounds bleomycin and cobalamin. On the basis of these structures, we propose that Rv1819c is a multi-solute transporter for hydrophilic molecules, analogous to the multidrug exporters of the ABC transporter family, which pump out structurally diverse hydrophobic compounds from cells8-11.

Asunto(s)

Transportadoras de Casetes de Unión a ATP/metabolismo; Proteínas Bacterianas/metabolismo; Bleomicina/metabolismo; Mycobacterium tuberculosis/metabolismo; Transportadoras de Casetes de Unión a ATP/química; Transportadoras de Casetes de Unión a ATP/genética; Proteínas Bacterianas/química; Proteínas Bacterianas/genética; Transporte Biológico; Interacciones Hidrofóbicas e Hidrofílicas; Modelos Moleculares; Mycobacterium tuberculosis/química; Mycobacterium tuberculosis/genética; Estructura Cuaternaria de Proteína; Estructura Terciaria de Proteína

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Bleomicina / Transportadoras de Casetes de Unión a ATP / Mycobacterium tuberculosis Idioma: En Revista: Nature Año: 2020 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido

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