2PZE

Minimal human CFTR first nucleotide binding domain as a head-to-tail dimer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.212 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant.

Atwell, S.Brouillette, C.G.Conners, K.Emtage, S.Gheyi, T.Guggino, W.B.Hendle, J.Hunt, J.F.Lewis, H.A.Lu, F.Protasevich, I.I.Rodgers, L.A.Romero, R.Wasserman, S.R.Weber, P.C.Wetmore, D.Zhang, F.F.Zhao, X.

(2010) Protein Eng Des Sel 23: 375-384

  • DOI: https://doi.org/10.1093/protein/gzq004
  • Primary Citation of Related Structures:  
    2PZE, 2PZF, 2PZG

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Eli Lilly & Co., 10300 Campus Point Drive, San Diego, CA 92121, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cystic fibrosis transmembrane conductance regulator
A, B
229Homo sapiensMutation(s): 1 
Gene Names: CFTRABCC7
UniProt & NIH Common Fund Data Resources
Find proteins for P13569 (Homo sapiens)
Explore P13569 
Go to UniProtKB:  P13569
PHAROS:  P13569
GTEx:  ENSG00000001626 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP13569
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
ATP Binding MOAD:  2PZE Kd: 840 (nM) from 1 assay(s)
PDBBind:  2PZE Kd: 840 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.212 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.803α = 90
b = 92.779β = 90
c = 107.419γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345data collection
MOSFLMdata reduction
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2007-10-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-08-16
    Changes: Refinement description, Source and taxonomy
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2018-11-14
    Changes: Data collection, Structure summary
  • Version 1.5: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description