Conformational Display: A Role for Switch Polymorphism in the Superfamily of Regulatory GTPases

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Science's STKE  19 Sep 2000:
Vol. 2000, Issue 50, pp. pe1
DOI: 10.1126/stke.2000.50.pe1


  • Fig. 1.

    Architecture of a Ras protein. (A) Ribbon diagram of the Mg2+·GppNHp complex of H-Ras (9); the P-loop (2, 3), which enfolds the nucleotide phosphates, is shown in blue, switch I is in magenta, and switch II and the α2 helix are in green. The Mg2+ is shown as a pale blue sphere. The nucleotide and selected amino acid side chains are shown as ball-and-stick models. Thr35 is a ligand of both Mg2+ and the γ phosphate in the GTP-bound state. Gln 61 is an essential catalytic residue that might serve to polarize and position the attacking water molecule in the transition state (2). (B) Carbon α traces of 20 structures derived from heteronuclear NMR of the GDP-bound form of H-Ras (10), shown with the same coloring scheme. The apparent dispersion of Cα trace near the two switch regions, but not the P-loop, is an indicator of the flexibility of these regions (see text).

  • Fig. 2.

    The environment of the active site and switch regions of Mg2+·GppNHp-Ran complex as bound to (A) importin β, and (B) Ran binding domain 1 of RanBP2 (see text). In the complex with importin β, the catalytic glutamine (Gln69) of Ran is rotated away from the catalytic site, possibly to avoid steric conflict with Phe72. In the RanBP2 complex, Gln69 adopts a conformation similar to that observed in Ras·GppNHp. The switch II segments in the two complexes adopt different conformations because of different constraints imposed by the bound effectors.

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