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7NF7

Ovine rBAT ectodomain homodimer, asymmetric unit

Summary for 7NF7
Entry DOI10.2210/pdb7nf7/pdb
EMDB information12297
Descriptorneutral and basic amino acid transport protein rBAT, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (4 entities in total)
Functional Keywordstransporter, cystinuria, complex, ectodomain, translocase
Biological sourceOvis aries (Sheep)
Total number of polymer chains1
Total formula weight80527.99
Authors
Lee, Y.,Kuehlbrandt, W. (deposition date: 2021-02-05, release date: 2022-01-19, Last modification date: 2024-11-06)
Primary citationLee, Y.,Wiriyasermkul, P.,Kongpracha, P.,Moriyama, S.,Mills, D.J.,Kuhlbrandt, W.,Nagamori, S.
Ca 2+ -mediated higher-order assembly of heterodimers in amino acid transport system b 0,+ biogenesis and cystinuria.
Nat Commun, 13:2708-2708, 2022
Cited by
PubMed Abstract: Cystinuria is a genetic disorder characterized by overexcretion of dibasic amino acids and cystine, causing recurrent kidney stones and kidney failure. Mutations of the regulatory glycoprotein rBAT and the amino acid transporter bAT, which constitute system b, are linked to type I and non-type I cystinuria respectively and they exhibit distinct phenotypes due to protein trafficking defects or catalytic inactivation. Here, using electron cryo-microscopy and biochemistry, we discover that Ca mediates higher-order assembly of system b. Ca stabilizes the interface between two rBAT molecules, leading to super-dimerization of bAT-rBAT, which in turn facilitates N-glycan maturation and protein trafficking. A cystinuria mutant T216M and mutations of the Ca site of rBAT cause the loss of higher-order assemblies, resulting in protein trapping at the ER and the loss of function. These results provide the molecular basis of system b biogenesis and type I cystinuria and serve as a guide to develop new therapeutic strategies against it. More broadly, our findings reveal an unprecedented link between transporter oligomeric assembly and protein-trafficking diseases.
PubMed: 35577790
DOI: 10.1038/s41467-022-30293-9
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.68 Å)
Structure validation

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PDB entries from 2024-11-06

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