ABCMdb

ABCC7 p.Gln1280Glu

Predicted by SNAP2:	A: N (61%), C: N (61%), D: N (61%), E: N (66%), F: N (57%), G: D (53%), H: N (97%), I: N (53%), K: N (78%), L: D (53%), M: N (66%), N: N (72%), P: D (53%), R: N (57%), S: N (66%), T: N (66%), V: N (57%), W: D (59%), Y: N (66%),
Predicted by PROVEAN:	A: N, C: D, D: N, E: N, F: N, G: D, H: N, I: D, K: N, L: N, M: N, N: N, P: N, R: N, S: N, T: N, V: N, W: D, Y: N,

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Publications
[hide] Cystic fibrosis transmembrane conductance regulato... Cold Spring Harb Perspect Med. 2013 Feb 1;3(2):a009514. doi: 10.1101/cshperspect.a009514. Hunt JF, Wang C, Ford RC
Cystic fibrosis transmembrane conductance regulator (ABCC7) structure.
Cold Spring Harb Perspect Med. 2013 Feb 1;3(2):a009514. doi: 10.1101/cshperspect.a009514., [PMID:23378596]

Abstract [show]
Structural studies of the cystic fibrosis transmembrane conductance regulator (CFTR) are reviewed. Like many membrane proteins, full-length CFTR has proven to be difficult to express and purify, hence much of the structural data available is for the more tractable, independently expressed soluble domains. Therefore, this chapter covers structural data for individual CFTR domains in addition to the sparser data available for the full-length protein. To set the context for these studies, we will start by reviewing structural information on model proteins from the ATP-binding cassette (ABC) transporter superfamily, to which CFTR belongs.

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289 Improvements in the yield of soluble protein were obtained by introducing the hydrolytically inactivating H1402A mutation in ATPase active site of hNBD2 plus a series of "solubilizing" mutations on its surface (Q1280E/ Y1307N/W1310H/Q1411D) (X Zhao, S Atwell, JF Hunt, et al., unpubl.). Login to comment

[hide] Regulatory R region of the CFTR chloride channel i... Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4427-36. doi: 10.1073/pnas.1315104110. Epub 2013 Nov 4. Bozoky Z, Krzeminski M, Muhandiram R, Birtley JR, Al-Zahrani A, Thomas PJ, Frizzell RA, Ford RC, Forman-Kay JD
Regulatory R region of the CFTR chloride channel is a dynamic integrator of phospho-dependent intra- and intermolecular interactions.
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4427-36. doi: 10.1073/pnas.1315104110. Epub 2013 Nov 4., [PMID:24191035]

Abstract [show]
Intrinsically disordered proteins play crucial roles in regulatory processes and often function as protein interaction hubs. Here, we present a detailed characterization of a full-length disordered hub protein region involved in multiple dynamic complexes. We performed NMR, CD, and fluorescence binding studies on the nonphosphorylated and highly PKA-phosphorylated human cystic fibrosis transmembrane conductance regulator (CFTR) regulatory region, a approximately 200-residue disordered segment involved in phosphorylation-dependent regulation of channel trafficking and gating. Our data provide evidence for dynamic, phosphorylation-dependent, multisite interactions of various segments of the regulatory region for its intra- and intermolecular partners, including the CFTR nucleotide binding domains 1 and 2, a 42-residue peptide from the C terminus of CFTR, the SLC26A3 sulphate transporter and antisigma factor antagonist (STAS) domain, and 14-3-3beta. Because of its large number of binding partners, multivalent binding of individually weak sites facilitates rapid exchange between free and bound states to allow the regulatory region to engage with different partners and generate a graded or rheostat-like response to phosphorylation. Our results enrich the understanding of how disordered binding segments interact with multiple targets. We present structural models consistent with our data that illustrate this dynamic aspect of phospho-regulation of CFTR by the disordered regulatory region.

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110 Binding was also probed to human CFTR NBD2 using a construct containing five solubilizing mutations (aa 1193-1445, Q1280E; Y1307N; Fig. 2. Login to comment
239 The NBD2 domain of human CFTR (aa 1193-1445, Q1280E; Y1307N; Q1411D; H1402A; and L1436D), a construct with solubilizing mutations designed by SGX, Inc., was encoded on a pET-SUMO plasmid (Invitrogen). Login to comment