In:
The EMBO Journal, EMBO, Vol. 42, No. 17 ( 2023-09-04)
Abstract:
image The human ABC transporter ABCC3/MRP3 transports diverse metabolites and drugs in multiple physiological processes. Here, both structural analysis and biochemical assays of ABCC3 are used to refine the common features of substrate‐binding pockets in multidrug resistance proteins. Three cryo‐EM structures of human ABCC3 are reported: the apo‐, E 2 17βG‐ and DHEAS‐bound forms. The two substrate‐bound ABCC3 complexes display a similar V‐shaped binding pocket, the hydrophobic center of which accommodates the steroid nuclei, whereas the hydrophilic patches stabilize the two conjugation groups of the substrate. The conjugation groups confer substrate specificity, and are coordinated by the conserved positively charged residues. A common substrate‐binding feature is proposed for all MRPs.
Type of Medium:
Online Resource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.2022113415
Language:
English
Publisher:
EMBO
Publication Date:
2023
detail.hit.zdb_id:
1467419-1
detail.hit.zdb_id:
586044-1
SSG:
12
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