[NMR paper] NMR Binding and Crystal Structure Reveal that Intrinsically-unstructured Regulatory Domain Auto-inhibits PAK4 by a Mechanism Different for that of PAK1.
NMR Binding and Crystal Structure Reveal that Intrinsically-unstructured Regulatory Domain Auto-inhibits PAK4 by a Mechanism Different for that of PAK1.
NMR Binding and Crystal Structure Reveal that Intrinsically-unstructured Regulatory Domain Auto-inhibits PAK4 by a Mechanism Different for that of PAK1.
Biochem Biophys Res Commun. 2013 Jul 19;
Authors: Wang W, Lim L, Baskaran Y, Manser E, Song J
Abstract
Six human PAK members are classified into groups I (PAKs 1-3) and II (PAK4-6). Previously, only group I PAKs were thought to be auto-inhibited but very recently PAK4, the prototype of group II PAKs, has also been shown to be auto-inhibited by its N-terminal regulatory domain. However, the complete auto-inhibitory domain (AID) sequence remains undefined and the mechanism underlying its auto-inhibition is largely elusive. Here, the N-terminal regulatory domain of PAK4 sufficient for auto-inhibiting and binding Cdc42/Rac was characterized to be intrinsically unstructured, but nevertheless we identified the entire AID sequence by NMR. Strikingly, an AID peptide was derived by deleting the binding-unnecessary residues, which has a Kd of 320 nM to the PAK4 catalytic domain. Consequently, the PAK4 crystal structure complexed with the entire AID has been determined, which reveals that the complete kinase cleft is occupied by 20 AID residues composed of an N-terminal ?-helix and a previously-identified pseudosubstrate motif, thus achieving auto-inhibition. Our study reveals that PAK4 is auto-inhibited by a novel mechanism which is completely different from that for PAK1, thus bearing critical implications for design of inhibitors specific for group II PAKs.
PMID: 23876315 [PubMed - as supplied by publisher]
[NMR paper] A new strategy for sequential assignment of intrinsically unstructured proteins based on 15N single isotope labelling
A new strategy for sequential assignment of intrinsically unstructured proteins based on 15N single isotope labelling
Publication date: Available online 23 July 2013
Source:Journal of Magnetic Resonance</br>
Author(s): Juan Lopez , Puneet Ahuja , Melanie Gérard , Jean Michel Wieruszeski , Guy Lippens</br>
We describe a new efficient strategy for the sequential assignment of amide resonances of a conventional 15N-1H HSQC spectrum of intrinsically unfolded proteins, based on composite NOESY-TOCSY and TOCSY-NOESY mixing times. These composite mixing times lead to a...
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The calponin regulatory region is intrinsically unstructured: novel insight into actin-calponin and calmodulin-calponin interfaces using NMR spectroscopy.
The calponin regulatory region is intrinsically unstructured: novel insight into actin-calponin and calmodulin-calponin interfaces using NMR spectroscopy.
The calponin regulatory region is intrinsically unstructured: novel insight into actin-calponin and calmodulin-calponin interfaces using NMR spectroscopy.
Biophys J. 2011 Apr 6;100(7):1718-28
Authors: Pfuhl M, Al-Sarayreh S, El-Mezgueldi M
Calponin is an actin- and calmodulin-binding protein believed to regulate the function of actin. Low-resolution studies based on proteolysis established that...
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04-06-2011 10:54 AM
Solution NMR and X-ray crystal structures of membrane-associated Lipoprotein-17 domain reveal a novel fold.
Solution NMR and X-ray crystal structures of membrane-associated Lipoprotein-17 domain reveal a novel fold.
Solution NMR and X-ray crystal structures of membrane-associated Lipoprotein-17 domain reveal a novel fold.
J Struct Funct Genomics. 2010 Dec 14;
Authors: Mani R, Vorobiev S, Swapna GV, Neely H, Janjua H, Ciccosanti C, Xiao R, Acton TB, Everett JK, Hunt J, Montelione GT
The conserved Lipoprotein-17 domain of membrane-associated protein Q9PRA0_UREPA from Ureaplasma parvum was selected for structure determination by the Northeast Structural...
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12-15-2010 12:03 PM
[NMR paper] NMR relaxation studies on the hydrate layer of intrinsically unstructured proteins.
NMR relaxation studies on the hydrate layer of intrinsically unstructured proteins.
Related Articles NMR relaxation studies on the hydrate layer of intrinsically unstructured proteins.
Biophys J. 2005 Mar;88(3):2030-7
Authors: Bokor M, Csizmók V, Kovács D, Bánki P, Friedrich P, Tompa P, Tompa K
Intrinsically unstructured/disordered proteins (IUPs) exist in a disordered and largely solvent-exposed, still functional, structural state under physiological conditions. As their function is often directly linked with structural disorder,...
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11-24-2010 10:03 PM
[NMR paper] NMR structure of the (1-51) N-terminal domain of the HIV-1 regulatory protein Vpr.
NMR structure of the (1-51) N-terminal domain of the HIV-1 regulatory protein Vpr.
Related Articles NMR structure of the (1-51) N-terminal domain of the HIV-1 regulatory protein Vpr.
Eur J Biochem. 1999 Dec;266(2):359-69
Authors: Wecker K, Roques BP
The human immunodeficiency virus type 1 (HIV-1) genome encodes a highly conserved 16 kDa regulatory gene product, Vpr (viral protein of regulation, 96 amino acid residues), which is incorporated into virions, in quantities equivalent to those of the viral Gag proteins. In the infected cells, Vpr is...
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11-18-2010 08:31 PM
[NMR paper] The negative-acting NMR regulatory protein of Neurospora crassa binds to and inhibits
The negative-acting NMR regulatory protein of Neurospora crassa binds to and inhibits the DNA-binding activity of the positive-acting nitrogen regulatory protein NIT2.
Related Articles The negative-acting NMR regulatory protein of Neurospora crassa binds to and inhibits the DNA-binding activity of the positive-acting nitrogen regulatory protein NIT2.
Biochemistry. 1995 Jul 11;34(27):8861-8
Authors: Xiao X, Fu YH, Marzluf GA
Structural genes of the nitrogen regulatory circuit of the filamentous fungus Neurospora crassa are under the control of...
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08-22-2010 03:50 AM
[NMR paper] Two crystal structures of the B1 immunoglobulin-binding domain of streptococcal prote
Two crystal structures of the B1 immunoglobulin-binding domain of streptococcal protein G and comparison with NMR.
Related Articles Two crystal structures of the B1 immunoglobulin-binding domain of streptococcal protein G and comparison with NMR.
Biochemistry. 1994 Apr 19;33(15):4721-9
Authors: Gallagher T, Alexander P, Bryan P, Gilliland GL
The structure of the 56-residue B1 immunoglobulin-binding domain from streptococcal protein G has been determined in two different crystal forms. The crystal structures were deduced by molecular...
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[NMR paper] NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein Vpr: m
NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein Vpr: molecular insights into its biological functions.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein Vpr: molecular insights into its biological functions.
J Mol Biol. 1999 Feb 5;285(5):2105-17
Authors: SchĂźler W, Wecker K, de Rocquigny H, Baudat Y, Sire J, Roques BP
The HIV-1 regulatory protein Vpr (96 amino...
NMR Binding and Crystal Structure Reveal that Intrinsically-unstructured Regulatory Domain Auto-inhibits PAK4 by a Mechanism Different for that of PAK1.
Linear Mode
