1XFA

Structure of NBD1 from murine CFTR- F508R mutant

Summary for 1XFA

• Entry DOI: 10.2210/pdb1xfa/pdb
• Related: 1XF9
• Descriptor: Cystic fibrosis transmembrane conductance regulator, MAGNESIUM ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: cystic fibrosis, abc transporters, atp, nucleotide-binding domain, transport protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Early endosome membrane; Multi-pass membrane protein (By similarity): P26361
• Total number of polymer chains: 2
• Total formula weight: 64932.17

Authors

Thibodeau, P.H.,Brautigam, C.A.,Machius, M.,Thomas, P.J. (deposition date: 2004-09-14, release date: 2004-12-28, Last modification date: 2023-08-23)

Primary citation

Thibodeau, P.H.,Brautigam, C.A.,Machius, M.,Thomas, P.J.
Side chain and backbone contributions of Phe508 to CFTR folding.
Nat.Struct.Mol.Biol., 12:10-16, 2005

PubMed Abstract: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

PubMed: 15619636
DOI: 10.1038/nsmb881

Experimental method

X-RAY DIFFRACTION (3.1 Å)