3DDC

Crystal Structure of NORE1A in Complex with RAS

Summary for 3DDC

• Entry DOI: 10.2210/pdb3ddc/pdb
• Descriptor: GTPase HRas, Ras association domain-containing family protein 5, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: 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
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side: P01112; Cytoplasm (By similarity): Q5EBH1
• Total number of polymer chains: 2
• Total formula weight: 37884.14

Authors

Stieglitz, B.,Bee, C.,Schwarz, D.,Yildiz, O.,Moshnikova, A.,Khokhlatchev, A.,Herrmann, C. (deposition date: 2008-06-05, release date: 2008-07-15, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)