ABCC7 p.Leu1436Asp
| Predicted by SNAP2: | A: N (78%), C: N (82%), D: N (61%), E: N (66%), F: N (93%), G: N (61%), H: N (87%), I: N (93%), K: N (72%), M: N (93%), N: N (66%), P: N (66%), Q: N (82%), R: N (82%), S: N (72%), T: N (82%), V: N (93%), W: N (66%), Y: N (93%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: D, H: N, I: N, K: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[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.
Comments [show]
None has been submitted yet.
No. Sentence Comment
117 Q1411D; L1436D; and H1402A) designed by SGX Inc. We find similar patterns of R region binding to NBD2 as for NBD1 (Fig. 1E), identifying NBD2 as a direct binding partner for R region and implying that the NBDs have similar binding properties.
X
ABCC7 p.Leu1436Asp 24191035:117:8
status: NEW239 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).
X
ABCC7 p.Leu1436Asp 24191035:239:81
status: NEW