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Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.

Publication ,  Journal Article
Johnston, CA; Lobanova, ES; Shavkunov, AS; Low, J; Ramer, JK; Blaesius, R; Fredericks, Z; Willard, FS; Kuhlman, B; Arshavsky, VY; Siderovski, DP
Published in: Biochemistry
September 26, 2006

G-proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G alpha subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069-1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP x AlF4(-)- and GTPgammaS-bound states of G alpha(i) subunits. KB-1753 blocks interaction of G alpha(transducin) with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated G alpha in vitro. The crystal structure of KB-1753 bound to G alpha(i1) x GDP x AlF4(-) reveals binding to a conserved hydrophobic groove between switch II and alpha3 helices and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for G alpha(i) subunits.

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Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

September 26, 2006

Volume

45

Issue

38

Start / End Page

11390 / 11400

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Recombinant Fusion Proteins
  • RGS Proteins
  • Protein Structure, Secondary
  • Protein Binding
  • Molecular Sequence Data
  • Models, Molecular
  • Luminescent Proteins
  • Humans
  • Guanosine Diphosphate
 

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Johnston, C. A., Lobanova, E. S., Shavkunov, A. S., Low, J., Ramer, J. K., Blaesius, R., … Siderovski, D. P. (2006). Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer. Biochemistry, 45(38), 11390–11400. https://doi.org/10.1021/bi0613832
Johnston, Christopher A., Ekaterina S. Lobanova, Alexander S. Shavkunov, Justin Low, J Kevin Ramer, Rainer Blaesius, Zoey Fredericks, et al. “Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.Biochemistry 45, no. 38 (September 26, 2006): 11390–400. https://doi.org/10.1021/bi0613832.
Johnston CA, Lobanova ES, Shavkunov AS, Low J, Ramer JK, Blaesius R, et al. Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer. Biochemistry. 2006 Sep 26;45(38):11390–400.
Johnston, Christopher A., et al. “Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.Biochemistry, vol. 45, no. 38, Sept. 2006, pp. 11390–400. Pubmed, doi:10.1021/bi0613832.
Johnston CA, Lobanova ES, Shavkunov AS, Low J, Ramer JK, Blaesius R, Fredericks Z, Willard FS, Kuhlman B, Arshavsky VY, Siderovski DP. Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer. Biochemistry. 2006 Sep 26;45(38):11390–11400.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

September 26, 2006

Volume

45

Issue

38

Start / End Page

11390 / 11400

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Recombinant Fusion Proteins
  • RGS Proteins
  • Protein Structure, Secondary
  • Protein Binding
  • Molecular Sequence Data
  • Models, Molecular
  • Luminescent Proteins
  • Humans
  • Guanosine Diphosphate