6BZS

Human ABCC6 NBD1 in Apo state

Summary for 6BZS

• Entry DOI: 10.2210/pdb6bzs/pdb
• Related: 6BZR
• Descriptor: Multidrug resistance-associated protein 6, SULFATE ION (3 entities in total)
• Functional Keywords: abcc6, nbd1, apo state, atp-binding cassette transporter c6, nucleotide binding domain 1, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 25404.96

Authors

Zheng, A.,Thibodeau, P.H. (deposition date: 2017-12-26, release date: 2018-09-05, Last modification date: 2023-10-04)

Primary citation

Ran, Y.,Zheng, A.,Thibodeau, P.H.
Structural analysis reveals pathomechanisms associated with pseudoxanthoma elasticum-causing mutations in the ABCC6 transporter.
J. Biol. Chem., 293:15855-15866, 2018

PubMed Abstract: Mutations in ABC subfamily C member 6 (ABCC6) transporter are associated with pseudoxanthoma elasticum (PXE), a disease resulting in ectopic mineralization and affecting multiple tissues. A growing number of mutations have been identified in individuals with PXE. For most of these variants, no mechanistic information is available regarding their role in normal and pathophysiologies. To assess how PXE-associated mutations alter ABCC6 biosynthesis and structure, we biophysically and biochemically evaluated the N-terminal nucleotide-binding domain. A high-resolution X-ray structure of nucleotide-binding domain 1 (NBD1) of human ABCC6 was obtained at 2.3 Å that provided a template on which to evaluate PXE-causing mutations. Biochemical analysis of mutations in this domain indicated that multiple PXE-causing mutations altered its structural properties. Analyses of the full-length protein revealed a strong correlation between the alterations in NBD properties and the processing and expression of ABCC6. These results suggest that a significant fraction of PXE-associated mutations located in NBD1 causes changes in its structural properties and that these mutation-induced alterations directly affect the maturation of the full-length ABCC6 protein.

PubMed: 30154241
DOI: 10.1074/jbc.RA118.004806

Experimental method

X-RAY DIFFRACTION (2.29990463032 Å)