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3D structure of the transporter ABCG2—What's new?

ABCG2 belongs to the ABC transporter superfamily and functions as a poly‐specific efflux pump. As it can transport a broad spectrum of substrates out of cells, ABCG2 is thought to alter the pharmacokinetics of drugs applied to treat certain diseases. Especially, its potential to induce resistance to...

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Detalles Bibliográficos
Autores principales: Eckenstaler, Robert, Benndorf, Ralf A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060357/
https://www.ncbi.nlm.nih.gov/pubmed/31985041
http://dx.doi.org/10.1111/bph.14991
Descripción
Sumario:ABCG2 belongs to the ABC transporter superfamily and functions as a poly‐specific efflux pump. As it can transport a broad spectrum of substrates out of cells, ABCG2 is thought to alter the pharmacokinetics of drugs applied to treat certain diseases. Especially, its potential to induce resistance to chemotherapy is currently the object of intense research. To foster understanding of mechanisms relevant for substrate recognition and selection of ABCG2 substrates and to finally develop selective therapeutic modulators (e.g. inhibitors) of ABCG2 transport activity, it is important to further explore the precise 3D structure of the transporter. While efforts to elucidate the three‐dimensional structure of ABCG2 using X‐ray crystal structure analysis have not been successful so far, high‐resolution cryo‐electron microscopy‐based investigations have revealed exciting new insights into the structure and function of the transporter. In this review, we will focus on these seminal publications to summarize the current understanding of tertiary and quaternary structure, homodimerization or oligomerization, and functions of the ABCG2 transporter protein.