7DPJ

H-Ras Q61L in complex with GppNHp (state 1) after structural transition by humidity control

Summary for 7DPJ

• Entry DOI: 10.2210/pdb7dpj/pdb
• Related: 7DPH
• Descriptor: GTPase HRas, MAGNESIUM ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: oncoprotein, state transition, ras
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 19962.72

Authors

Taniguchi, H.,Matsumoto, S.,Miyamoto, R.,Kawamura, T.,Kumasaka, T.,Kataoka, T. (deposition date: 2020-12-19, release date: 2021-07-28, Last modification date: 2023-11-29)

Primary citation

Matsumoto, S.,Taniguchi-Tamura, H.,Araki, M.,Kawamura, T.,Miyamoto, R.,Tsuda, C.,Shima, F.,Kumasaka, T.,Okuno, Y.,Kataoka, T.
Oncogenic mutations Q61L and Q61H confer active form-like structural features to the inactive state (state 1) conformation of H-Ras protein.
Biochem.Biophys.Res.Commun., 565:85-90, 2021

PubMed Abstract: GTP-bound forms of Ras proteins (Ras•GTP) assume two interconverting conformations, "inactive" state 1 and "active" state 2. Our previous study on the crystal structure of the state 1 conformation of H-Ras in complex with guanosine 5'-(β, γ-imido)triphosphate (GppNHp) indicated that state 1 is stabilized by intramolecular hydrogen-bonding interactions formed by Gln61. Since Ras are constitutively activated by substitution mutations of Gln61, here we determine crystal structures of the state 1 conformation of H-Ras•GppNHp carrying representative mutations Q61L and Q61H to observe the effect of the mutations. The results show that these mutations alter the mode of hydrogen-bonding interactions of the residue 61 with Switch II residues and induce conformational destabilization of the neighboring regions. In particular, Q61L mutation results in acquirement of state 2-like structural features. Moreover, the mutations are likely to impair an intramolecular structural communication between Switch I and Switch II. Molecular dynamics simulations starting from these structures support the above observations. These findings may give a new insight into the molecular mechanism underlying the aberrant activation of the Gln61 mutants.

PubMed: 34102474
DOI: 10.1016/j.bbrc.2021.05.084

Experimental method

X-RAY DIFFRACTION (1.976 Å)