G Protein Coupled Receptors

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G Protein Coupled Receptors

• Tim Hulsen
• David Lutje Hulsik

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G Protein Coupled Receptors

• seven transmembrane regions
• hydrophobic/ hydrophilic domains
• conserved residues and motifs (i.e. NPXXY)

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Major research difficulties

• Residue numbering Schwartz / Baldwin
• (e.g. V.16)
• Ballesteros-Weinstein
• (e.g. 6.50)
• High-resolution structural information

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Many possible methods

• mutation studies
• spinlabel
• NMR
• cystein scanning
• protease studies
• photoaffinity

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Novel approaches (1)

• Turcatti et al. (1996) introducing unnatural
  amino acids at known sites by suppression of UAG
  nonsense codons with the aid of a chemically
  misacetylated synthetic tRNA ? determination of
  distances by measuring the fluorescence resonance
  energy transfer (FRET) between the fluorescent
  unnatural amino acids ? defining of structure

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Novel approaches (2)

• Gröbner, G. et al. (2000) determination of
  three-dimensional structure using a new
  high-resolution solid-state NMR method deuterium
  (2H) NMR in combination with the magic angle
  oriented sample spinning (MAOSS) approach.