spacer
spacer
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Signaling protein PDB id
2g83
Jmol
Contents
Protein chains
303 a.a. *
11 a.a. *
Ligands
ALF ×2
GDP ×2
Metals
_MG ×2
Waters ×30
* Residue conservation analysis
PDB id:
2g83
Name: Signaling protein
Title: Structure of activated g-alpha-i1 bound to a nucleotide- state-selective peptide: minimal determinants for recognizing the active form of a g protein alpha subunit
Structure: Guanine nucleotide-binding protein g(i), alpha-1 subunit. Chain: a, b. Synonym: adenylate cyclase-inhibiting g alpha protein. Engineered: yes. Kb-1753 phage display peptide. Chain: c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gnai1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: phage-derived peptide
Biol. unit: Dimer (from PQS)
Resolution:
2.80Å     R-factor:   0.269     R-free:   0.300
Authors: C.A.Johnston,J.K.Ramer,R.Blaesius,B.Kuhlman,V.Y.Arshavsky, D.P.Siderovski
Key ref:
C.A.Johnston et al. (2006). Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer. Biochemistry, 45, 11390-11400. PubMed id: 16981699 DOI: 10.1021/bi0613832
Date:
01-Mar-06     Release date:   10-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P63096  (GNAI1_HUMAN) -  Guanine nucleotide-binding protein G(i) subunit alpha-1
Seq:
Struc: 		354 a.a.
303 a.a.
Protein chain
No UniProt id for this chain
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   2 terms 
  Biochemical function     signal transducer activity     3 terms  

 

 
DOI no: 10.1021/bi0613832 Biochemistry 45:11390-11400 (2006)
PubMed id: 16981699  
 
 
Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.
C.A.Johnston, E.S.Lobanova, A.S.Shavkunov, J.Low, J.K.Ramer, R.Blaesius, Z.Fredericks, F.S.Willard, B.Kuhlman, V.Y.Arshavsky, D.P.Siderovski.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20351284 N.A.Lambert, C.A.Johnston, S.D.Cappell, S.Kuravi, A.J.Kimple, F.S.Willard, and D.P.Siderovski (2010).
Regulators of G-protein signaling accelerate GPCR signaling kinetics and govern sensitivity solely by accelerating GTPase activity.
  Proc Natl Acad Sci U S A, 107, 7066-7071.  
20662737 R.E.Muller, K.R.Klein, S.Q.Hutsell, D.P.Siderovski, and A.J.Kimple (2010).
A homogeneous method to measure nucleotide exchange by α-subunits of heterotrimeric G-proteins using fluorescence polarization.
  Assay Drug Dev Technol, 8, 621-624.  
  20217614 S.Q.Hutsell, R.J.Kimple, D.P.Siderovski, F.S.Willard, and A.J.Kimple (2010).
High-affinity immobilization of proteins using biotin- and GST-based coupling strategies.
  Methods Mol Biol, 627, 75-90.  
19222191 A.M.Preininger, M.A.Funk, W.M.Oldham, S.M.Meier, C.A.Johnston, S.Adhikary, A.J.Kimple, D.P.Siderovski, H.E.Hamm, and T.M.Iverson (2009).
Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits.
  Biochemistry, 48, 2630-2642.
PDB code: 3d7m
19820068 T.Zielinski, A.J.Kimple, S.Q.Hutsell, M.D.Koeff, D.P.Siderovski, and R.G.Lowery (2009).
Two Galpha(i1) rate-modifying mutations act in concert to allow receptor-independent, steady-state measurements of RGS protein activity.
  J Biomol Screen, 14, 1195-1206.  
18537558 C.A.Johnston, F.S.Willard, J.K.Ramer, R.Blaesius, C.N.Roques, and D.P.Siderovski (2008).
State-selective binding peptides for heterotrimeric G-protein subunits: novel tools for investigating G-protein signaling dynamics.
  Comb Chem High Throughput Screen, 11, 370-381.  
18519563 C.A.Johnston, K.Afshar, J.T.Snyder, G.G.Tall, P.Gönczy, D.P.Siderovski, and F.S.Willard (2008).
Structural determinants underlying the temperature-sensitive nature of a Galpha mutant in asymmetric cell division of Caenorhabditis elegans.
  J Biol Chem, 283, 21550-21558.
PDB code: 2ebc
18984596 F.S.Willard, Z.Zheng, J.Guo, G.J.Digby, A.J.Kimple, J.M.Conley, C.A.Johnston, D.Bosch, M.D.Willard, V.J.Watts, N.A.Lambert, S.R.Ikeda, Q.Du, and D.P.Siderovski (2008).
A Point Mutation to G{alpha}i Selectively Blocks GoLoco Motif Binding: DIRECT EVIDENCE FOR G{alpha}{middle dot}GoLoco COMPLEXES IN MITOTIC SPINDLE DYNAMICS.
  J Biol Chem, 283, 36698-36710.  
18434541 M.Soundararajan, F.S.Willard, A.J.Kimple, A.P.Turnbull, L.J.Ball, G.A.Schoch, C.Gileadi, O.Y.Fedorov, E.F.Dowler, V.A.Higman, S.Q.Hutsell, M.Sundström, D.A.Doyle, and D.P.Siderovski (2008).
Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.
  Proc Natl Acad Sci U S A, 105, 6457-6462.
PDB codes: 1zv4 2a72 2af0 2bt2 2bv1 2es0 2gtp 2i59 2ihb 2ihd 2ik8 2jm5 2jnu 2ode 2owi
18329041 R.J.Austin, W.W.Ja, and R.W.Roberts (2008).
Evolution of class-specific peptides targeting a hot spot of the Galphas subunit.
  J Mol Biol, 377, 1406-1418.  
17603074 D.W.Sammond, Z.M.Eletr, C.Purbeck, R.J.Kimple, D.P.Siderovski, and B.Kuhlman (2007).
Structure-based protocol for identifying mutations that enhance protein-protein binding affinities.
  J Mol Biol, 371, 1392-1404.
PDB code: 2om2
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.