5B2Z: H-ras Wt In Complex With Gppnhp (state 2*) Before Structural Transition By Humidity Control

Ras*GTP adopts two interconverting conformational states, state 1 and state 2, corresponding to inactive and active forms, respectively. However, analysis of the mechanism for state transition was hampered by the lack of the structural information on wild-type Ras state 1 despite its fundamental nature conserved in the Ras superfamily. Here we solve two new crystal structures of wild-type H-Ras, corresponding to state 1 and state 2. The state 2 structure seems to represent an intermediate of state transition and, intriguingly, the state 1 crystal is successfully derived from this state 2 crystal by regulating the surrounding humidity. Structural comparison enables us to infer the molecular mechanism for state transition, during which a wide range of hydrogen-bonding networks across Switch I, Switch II and the alpha3-helix interdependently undergo gross rearrangements, where fluctuation of Tyr32, translocation of Gln61, loss of the functional water molecules and positional shift of GTP play major roles. The NMR-based hydrogen/deuterium exchange experiments also support this transition mechanism. Moreover, the unveiled structural features together with the results of the biochemical study provide a new insight into the physiological role of state 1 as a stable pool of Ras*GTP in the GDP/GTP cycle of Ras.
PDB ID: 5B2ZDownload
MMDB ID: 139678
PDB Deposition Date: 2016/2/7
Updated in MMDB: 2016/06
Experimental Method:
x-ray diffraction
Resolution: 1.56  Å
Source Organism:
Similar Structures:
Biological Unit for 5B2Z: monomeric; determined by author and by software (PISA)
Molecular Components in 5B2Z
Label Count Molecule
Protein (1 molecule)
Gtpase Hras(Gene symbol: HRAS)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

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