PDBsum entry 1xf9

Transport protein

PDB id: 1xf9

Contents

Protein chains

264 a.a. *

Ligands

ATP ×4

ACY ×6

Metals

_MG ×7

Waters ×155

* Residue conservation analysis

PDB id:

1xf9

Name:

Transport protein

Title:

Structure of nbd1 from murine cftr- f508s mutant

Structure:

Cystic fibrosis transmembrane conductance regulator. Chain: a, b, c, d. Fragment: nbd1. Synonym: cftr, camp-dependent chloride channel. Engineered: yes. Mutation: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: cftr, abcc7. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Octamer (from PQS)

Resolution:

2.70Å R-factor: 0.201 R-free: 0.253

Authors:

P.H.Thibodeau,C.A.Brautigam,M.Machius,P.J.Thomas

Key ref:

P.H.Thibodeau et al. (2005). Side chain and backbone contributions of Phe508 to CFTR folding. Nat Struct Mol Biol, 12, 10-16. PubMed id: 15619636 DOI: 10.1038/nsmb881

Date:

14-Sep-04 Release date: 28-Dec-04

Protein chains

P26361  (CFTR_MOUSE) -  Cystic fibrosis transmembrane conductance regulator from Mus musculus

Seq: 1476 a.a.

Struc: 264 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.5.6.1.6 - channel-conductance-controlling ATPase.
• Reaction: ATP + H2O + closed Cl^- channel = ADP + phosphate + open Cl^- channel

ATP (Bound ligand (Het Group name = ATP) corresponds exactly) + H2O + closed Cl(-) channel = ADP + phosphate + open Cl(-) channel

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/nsmb881

Nat Struct Mol Biol 12:10-16 (2005)

PubMed id: 15619636

Side chain and backbone contributions of Phe508 to CFTR folding.

P.H.Thibodeau, C.A.Brautigam, M.Machius, P.J.Thomas.

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.

Selected figure(s)

Figure 3.
Figure 3. Maturation of full-length CFTR mutants.

Figure 4.
Figure 4. ABC transporter structure and CFTR biogenesis. (a) Crystal structure of the BtuCD ABC-transport systems21. The Escherichia coli vitamin D transporter system BtuCD structures (PDB entry 1L7V) are shown with the Phe508-analogous residue Leu96 shown in red spheres at the NBD-TMD interfaces. The BtuC transmembrane proteins are blue and the BtuD NBDs are yellow. Two views of the BtuCD complex are shown rotated about the vertical axis by 90°. (b) Hierarchical folding of CFTR. Step 1, TMD1 is translated and inserted into the membrane. Pale blue indicates the reduced stability of TMD1 in the absence of NBD1. Step 2, NBD1 is translated and folds into a native or near-native state. The blurred image of the mNBD1 structure indicates the attainment of a native or near-native state, which is most likely stabilized by interactions with additional CFTR domains. Step 3, NBD1 docks against TMD1. This event probably leads to the stabilization of both NBD1 and TMD1, as shown by the change in blue color in the TMD and the sharpening of the NBD1 structure. This is followed by the translation, folding and assembly of the domains C-terminal to NBD1. Mutations that putatively affect each step are in parentheses. The NBDs are represented by the mNBD1 structure and are oriented relative to the NBD dimer and TMD -NBD complex seen in BtuCD with the assumption that CFTR is monomeric with a functional NBD1 -NBD2 heterodimer.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 10-16) copyright 2005.

Figures were selected by an automated process.