PDBsum entry 2pzf

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chain
224 a.a. *
ATP ×2
_MG ×2
Waters ×130
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Minimal human cftr first nucleotide binding domain as a head dimer with delta f508
Structure: Cystic fibrosis transmembrane conductance regulat chain: a, b. Fragment: cftr nbd1 387-646(del405-436,delf508). Synonym: cftr, camp- dependent chloride channel, atp-bindin transporter sub- family c member 7. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cftr, abcc7. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.213     R-free:   0.251
Authors: S.Atwell,K.Conners,S.Emtage,T.Gheyi,N.R.Glenn,J.Hendle,H.A.L F.Lu,L.A.Rodgers,R.Romero,J.M.Sauder,D.Smith,H.Tien,S.R.Was X.Zhao
Key ref: S.Atwell et al. (2010). Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant. Protein Eng Des Sel, 23, 375-384. PubMed id: 20150177
18-May-07     Release date:   09-Oct-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P13569  (CFTR_HUMAN) -  Cystic fibrosis transmembrane conductance regulator
1480 a.a.
224 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     ATP binding     2 terms  


Protein Eng Des Sel 23:375-384 (2010)
PubMed id: 20150177  
Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant.
S.Atwell, C.G.Brouillette, K.Conners, S.Emtage, T.Gheyi, W.B.Guggino, J.Hendle, J.F.Hunt, H.A.Lewis, F.Lu, I.I.Protasevich, L.A.Rodgers, R.Romero, S.R.Wasserman, P.C.Weber, D.Wetmore, F.F.Zhang, X.Zhao.
Upon removal of the regulatory insert (RI), the first nucleotide binding domain (NBD1) of human cystic fibrosis transmembrane conductance regulator (CFTR) can be heterologously expressed and purified in a form that remains stable without solubilizing mutations, stabilizing agents or the regulatory extension (RE). This protein, NBD1 387-646(Delta405-436), crystallizes as a homodimer with a head-to-tail association equivalent to the active conformation observed for NBDs from symmetric ATP transporters. The 1.7-A resolution X-ray structure shows how ATP occupies the signature LSGGQ half-site in CFTR NBD1. The DeltaF508 version of this protein also crystallizes as a homodimer and differs from the wild-type structure only in the vicinity of the disease-causing F508 deletion. A slightly longer construct crystallizes as a monomer. Comparisons of the homodimer structure with this and previously published monomeric structures show that the main effect of ATP binding at the signature site is to order the residues immediately preceding the signature sequence, residues 542-547, in a conformation compatible with nucleotide binding. These residues likely interact with a transmembrane domain intracellular loop in the full-length CFTR channel. The experiments described here show that removing the RI from NBD1 converts it into a well-behaved protein amenable to biophysical studies yielding deeper insights into CFTR function.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20855293 B.Meineke, B.Schwer, R.Schaffrath, and S.Shuman (2011).
Determinants of eukaryal cell killing by the bacterial ribotoxin PrrC.
  Nucleic Acids Res, 39, 687-700.  
21275046 E.Noy, and H.Senderowitz (2011).
Combating cystic fibrosis: in search for CF transmembrane conductance regulator (CFTR) modulators.
  ChemMedChem, 6, 243-251.  
20687163 C.Wang, I.Protasevich, Z.Yang, D.Seehausen, T.Skalak, X.Zhao, S.Atwell, J.Spencer Emtage, D.R.Wetmore, C.G.Brouillette, and J.F.Hunt (2010).
Integrated biophysical studies implicate partial unfolding of NBD1 of CFTR in the molecular pathogenesis of F508del cystic fibrosis.
  Protein Sci, 19, 1932-1947.  
21152102 H.Hoelen, B.Kleizen, A.Schmidt, J.Richardson, P.Charitou, P.J.Thomas, and I.Braakman (2010).
The primary folding defect and rescue of ΔF508 CFTR emerge during translation of the mutant domain.
  PLoS One, 5, e15458.  
20687133 I.Protasevich, Z.Yang, C.Wang, S.Atwell, X.Zhao, S.Emtage, D.Wetmore, J.F.Hunt, and C.G.Brouillette (2010).
Thermal unfolding studies show the disease causing F508del mutation in CFTR thermodynamically destabilizes nucleotide-binding domain 1.
  Protein Sci, 19, 1917-1931.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.