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PDBsum entry 2pze
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References listed in PDB file
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Key reference
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Title
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Structures of a minimal human cftr first nucleotide-Binding domain as a monomer, Head-To-Tail homodimer, And pathogenic mutant.
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Authors
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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.
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Ref.
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Protein Eng Des Sel, 2010,
23,
375-384.
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PubMed id
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Abstract
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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.
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Secondary reference #1
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Title
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Abstracts of the 21st annual north american cystic fibrosis conference, October 3-6, 2007, Anaheim, California, Usa.
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Authors
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S.Atwell,
K.Conners,
S.Emtage,
T.Gheyi,
H.Lewis,
F.Lu,
R.Romero,
X.Zhao.
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Ref.
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Pediatr Pulmonol Suppl, 2007,
30,
99-101.
[DOI no: ]
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PubMed id
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