6Q21

MOLECULAR SWITCH FOR SIGNAL TRANSDUCTION: STRUCTURAL DIFFERENCES BETWEEN ACTIVE AND INACTIVE FORMS OF PROTOONCOGENIC RAS PROTEINS

6Q21 の概要

• エントリーDOI: 10.2210/pdb6q21/pdb
• 分子名称: C-H-RAS P21 PROTEIN CATALYTIC DOMAIN, MAGNESIUM ION, PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER, ... (4 entities in total)
• 機能のキーワード: oncogene protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane. Isoform 2: Nucleus: P01112
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 80250.30

構造登録者

Kim, S.-H. (登録日: 1992-07-27, 公開日: 1992-07-28, 最終更新日: 2024-03-13)

主引用文献

Milburn, M.V.,Tong, L.,deVos, A.M.,Brunger, A.,Yamaizumi, Z.,Nishimura, S.,Kim, S.H.
Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins.
Science, 247:939-945, 1990

PubMed Abstract: Ras proteins participate as a molecular switch in the early steps of the signal transduction pathway that is associated with cell growth and differentiation. When the protein is in its GTP complexed form it is active in signal transduction, whereas it is inactive in its GDP complexed form. A comparison of eight three-dimensional structures of ras proteins in four different crystal lattices, five with a nonhydrolyzable GTP analog and three with GDP, reveals that the "on" and "off" states of the switch are distinguished by conformational differences that span a length of more than 40 A, and are induced by the gamma-phosphate. The most significant differences are localized in two regions: residues 30 to 38 (the switch I region) in the second loop and residues 60 to 76 (the switch II region) consisting of the fourth loop and the short alpha-helix that follows the loop. Both regions are highly exposed and form a continuous strip on the molecular surface most likely to be the recognition sites for the effector and receptor molecule(or molecules). The conformational differences also provide a structural basis for understanding the biological and biochemical changes of the proteins due to oncogenic mutations, autophosphorylation, and GTP hydrolysis, and for understanding the interactions with other proteins.

PubMed: 2406906

実験手法

X-RAY DIFFRACTION (1.95 Å)