5X9S

Crystal structure of fully modified H-Ras-GppNHp

Summary for 5X9S

• Entry DOI: 10.2210/pdb5x9s/pdb
• Descriptor: GTPase HRas, MAGNESIUM ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: oncoprotein
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane. Isoform 2: Nucleus: P01112
• Total number of polymer chains: 1
• Total formula weight: 22041.67

Authors

Matsumoto, S.,Ke, H.,Murashima, Y.,Taniguchi-Tamura, H.,Miyamoto, R.,Yoshikawa, Y.,Kumasaka, T.,Mizohata, E.,Edamatsu, H.,Kataoka, T. (deposition date: 2017-03-09, release date: 2017-08-30, Last modification date: 2023-11-22)

Primary citation

Ke, H.,Matsumoto, S.,Murashima, Y.,Taniguchi-Tamura, H.,Miyamoto, R.,Yoshikawa, Y.,Tsuda, C.,Kumasaka, T.,Mizohata, E.,Edamatsu, H.,Kataoka, T.
Structural basis for intramolecular interaction of post-translationally modified H-RasGTP prepared by protein ligation
FEBS Lett., 591:2470-2481, 2017

PubMed Abstract: Ras undergoes post-translational modifications including farnesylation, proteolysis, and carboxymethylation at the C terminus, which are necessary for membrane recruitment and effector recognition. Full activation of c-Raf-1 requires cooperative interaction of the farnesylated C terminus and the activator region of Ras with its cysteine-rich domain (CRD). However, the molecular basis for this interaction remains unclear because of difficulties in preparing modified Ras in amounts sufficient for structural studies. Here, we use Sortase A-catalyzed protein ligation to prepare modified Ras in sufficient amounts for NMR and X-ray crystallographic analyses. The results show that the farnesylated C terminus establishes an intramolecular interaction with the catalytic domain and brings the farnesyl moiety to the proximity of the activator region, which may be responsible for their cooperative recognition of c-Raf-1-CRD.

PubMed: 28730604
DOI: 10.1002/1873-3468.12759

Experimental method

X-RAY DIFFRACTION (2.5 Å)