3DDC

Crystal Structure of NORE1A in Complex with RAS

3DDC の概要

• エントリーDOI: 10.2210/pdb3ddc/pdb
• 分子名称: GTPase HRas, Ras association domain-containing family protein 5, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: oncogene, tumorsuppressor, ubiquitin fold, ras effector, rap1, h-ras, rassf1, rassf5, rapl, nore1, gmppnp, adaptor, apoptosis, microtubules, hydrolase-apoptosis complex, disease mutation, golgi apparatus, gtp-binding, lipoprotein, membrane, methylation, nucleotide-binding, palmitate, prenylation, proto-oncogene, anti-oncogene, cell cycle, metal-binding, microtubule, phorbol-ester binding, zinc-finger, hydrolase/apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side: P01112; Cytoplasm (By similarity): Q5EBH1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37884.14

構造登録者

Stieglitz, B.,Bee, C.,Schwarz, D.,Yildiz, O.,Moshnikova, A.,Khokhlatchev, A.,Herrmann, C. (登録日: 2008-06-05, 公開日: 2008-07-15, 最終更新日: 2023-11-01)

主引用文献

Stieglitz, B.,Bee, C.,Schwarz, D.,Yildiz, O.,Moshnikova, A.,Khokhlatchev, A.,Herrmann, C.
Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II
Embo J., 27:1995-2005, 2008

PubMed Abstract: A class of putative Ras effectors called Ras association domain family (RASSF) represents non-enzymatic adaptors that were shown to be important in tumour suppression. RASSF5, a member of this family, exists in two splice variants known as NORE1A and RAPL. Both of them are involved in distinct cellular pathways triggered by Ras and Rap, respectively. Here we describe the crystal structure of Ras in complex with the Ras binding domain (RBD) of NORE1A/RAPL. All Ras effectors share a common topology in their RBD creating an interface with the switch I region of Ras, whereas NORE1A/RAPL RBD reveals additional structural elements forming a unique Ras switch II binding site. Consequently, the contact area of NORE1A is extended as compared with other Ras effectors. We demonstrate that the enlarged interface provides a rationale for an exceptionally long lifetime of the complex. This is a specific attribute characterizing the effector function of NORE1A/RAPL as adaptors, in contrast to classical enzymatic effectors such as Raf, RalGDS or PI3K, which are known to form highly dynamic short-lived complexes with Ras.

PubMed: 18596699
DOI: 10.1038/emboj.2008.125

実験手法

X-RAY DIFFRACTION (1.8 Å)