Related ArticlesDimeric switch of Hakai-truncated monomers during substrate recognition: insights from solution studies and NMR structure.
J Biol Chem. 2014 Sep 12;289(37):25611-23
Authors: Mukherjee M, Jing-Song F, Ramachandran S, Guy GR, Sivaraman J
Abstract
Hakai, an E3 ubiquitin ligase, disrupts cell-cell contacts in epithelial cells and is up-regulated in human colon and gastric adenocarcinomas. Hakai acts through its phosphotyrosine-binding (HYB) domain, which bears a dimeric fold that recognizes the phosphotyrosine motifs of E-cadherin, cortactin, DOK1, and other Src substrates. Unlike the monomeric nature of the SH2 and phosphotyrosine-binding domains, the architecture of the HYB domain consists of an atypical, zinc-coordinated tight homodimer. Here, we report a C-terminal truncation mutant of the HYB domain (HYB(?C)), comprising amino acids 106-194, which exists as a monomer in solution. The NMR structure revealed that this deletion mutant undergoes a dramatic structural change caused by a rearrangement of the atypical zinc-coordinated unit in the C terminus of the HYB domain to a C2H2-like zinc finger in HYB(?C). Moreover, using isothermal titration calorimetry, we show that dimerization of HYB(?C) can be induced using a phosphotyrosine substrate peptide. This ligand-induced dimerization of HYB(?C) is further validated using analytical ultracentrifugation, size-exclusion chromatography, NMR relaxation studies, dynamic light scattering, and circular dichroism experiments. Overall, these observations suggest that the dimeric architecture of the HYB domain is essential for the phosphotyrosine-binding property of Hakai.
Structure and Dynamicsof Mycobacterium tuberculosis Truncated HemoglobinN: Insights from NMR Spectroscopy and MolecularDynamics Simulations
Structure and Dynamicsof Mycobacterium tuberculosis Truncated HemoglobinN: Insights from NMR Spectroscopy and MolecularDynamics Simulations
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/0/bichaw.ahead-of-print/bi201059a/aop/images/medium/bi-2011-01059a_0006.gif
Biochemistry
DOI: 10.1021/bi201059a
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Transient Enzyme–Substrate Recognition Monitored by Real-Time NMR
Transient Enzyme–Substrate Recognition Monitored by Real-Time NMR
Caroline Haupt, Rica Patzschke, Ulrich Weininger, Stefan Gro?ger, Michael Kovermann and Jochen Balbach
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja2010048/aop/images/medium/ja-2011-010048_0002.gif
Journal of the American Chemical Society
DOI: 10.1021/ja2010048
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06-30-2011 05:01 AM
Transient enzyme-substrate recognition monitored by real-time NMR.
Transient enzyme-substrate recognition monitored by real-time NMR.
Transient enzyme-substrate recognition monitored by real-time NMR.
J Am Chem Soc. 2011 Jun 10;
Authors: Haupt C, Patzschke R, Weininger U, Gröger S, Kovermann M, Balbach J
Slow protein folding processes during which kinetic folding intermediates occur for an extended time can lead to aggregation and dysfunction in living cells. Therefore protein folding helpers have evolved, which prevent proteins from aggregation and/ or speed up folding processes. In this study we present the...
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06-15-2011 01:15 PM
The NMR Structure of FliK, the Trigger for the Switch of Substrate Specificity in the Flagellar Type III Secretion Apparatus.
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The NMR Structure of FliK, the Trigger for the Switch of Substrate Specificity in the Flagellar Type III Secretion Apparatus.
J Mol Biol. 2011 Apr 12;
Authors: Mizuno S, Amida H, Kobayashi N, Aizawa SI, Tate SI
The flagellar cytoplasmic protein FliK controls hook elongation by two successive events: by determining hook length and by stopping the supply of hook protein. These two distinct roles are assigned to different...
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04-25-2011 11:53 AM
Solution 1H NMR characterization of substrate-free C. diphtheriae heme oxygenase: pertinence for determining magnetic axes in paramagnetic substrate complexes.
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Solution 1H NMR characterization of substrate-free C. diphtheriae heme oxygenase: pertinence for determining magnetic axes in paramagnetic substrate complexes.
J Inorg Biochem. 2010 Oct;104(10):1063-70
Authors: Du Z, Unno M, Matsui T, Ikeda-Saito M, La Mar GN
Proton 2D NMR was used to confirm in solution a highly conserved portion of the molecular structure upon substrate loss for the...
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02-10-2011 03:51 PM
[NMR paper] Substrate recognition by the Lyn protein-tyrosine kinase. NMR structure of the immuno
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Authors: Gaul BS, Harrison ML, Geahlen RL, Burton RA, Post CB
The immunoreceptor tyrosine-based activation motif (ITAM) plays a central role...
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11-18-2010 09:15 PM
[NMR paper] NMR structural studies of human cystatin C dimers and monomers.
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http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles NMR structural studies of human cystatin C dimers and monomers.
J Mol Biol. 1997 Aug 15;271(2):266-77
Authors: Ekiel I, Abrahamson M, Fulton DB, Lindahl P, Storer AC, Levadoux W, Lafrance M, Labelle S, Pomerleau Y, Groleau D, LeSauteur L, Gehring K
Human cystatin C undergoes dimerization before unfolding. Dimerization leads to a complete loss of its activity...
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08-22-2010 05:08 PM
[NMR paper] Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent pro
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J Pept Res. 1997 Mar;49(3):210-20
Authors: Padilla A, Hauer JA, Tsigelny I, Parello J, Taylor SS
Peptides derived from the inhibitor of cAMP-dependent protein kinase. PKI, have been studied by 2D 1H NMR techniques. These include the inhibitor...
Dimeric switch of Hakai-truncated monomers during substrate recognition: insights from solution studies and NMR structure.
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