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PDBsum entry 3ddc

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protein ligands metals Protein-protein interface(s) links
Hydrolase/apoptosis PDB id
3ddc
Jmol PyMol
Contents
Protein chains
166 a.a. *
133 a.a. *
Ligands
GNP
Metals
_MG
Waters ×115
* Residue conservation analysis
PDB id:
3ddc
Name: Hydrolase/apoptosis
Title: Crystal structure of nore1a in complex with ras
Structure: Gtpase hras. Chain: a. Fragment: unp residues 1-166. Synonym: transforming protein p21, p21ras, h-ras-1, c-h-ras engineered: yes. Mutation: yes. Ras association domain-containing family protein chain: b. Fragment: ras binding domain, unp residues 200-358.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hras, hras1. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. Mouse. Organism_taxid: 10090.
Resolution:
1.80Å     R-factor:   0.195     R-free:   0.230
Authors: B.Stieglitz,C.Bee,D.Schwarz,O.Yildiz,A.Moshnikova,A.Khokhlat C.Herrmann
Key ref: B.Stieglitz et al. (2008). Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II. EMBO J, 27, 1995-2005. PubMed id: 18596699 DOI: 10.1038/emboj.2008.125
Date:
05-Jun-08     Release date:   15-Jul-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01112  (RASH_HUMAN) -  GTPase HRas
Seq:
Struc:
189 a.a.
166 a.a.*
Protein chain
Pfam   ArchSchema ?
Q5EBH1  (RASF5_MOUSE) -  Ras association domain-containing protein 5
Seq:
Struc:
413 a.a.
133 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.3.6.5.2  - Small monomeric GTPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: GTP + H2O = GDP + phosphate
GTP
+ H(2)O
=
GDP
Bound ligand (Het Group name = GNP)
matches with 81.82% similarity
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     signal transduction   3 terms 
  Biochemical function     GTP binding     2 terms  

 

 
    reference    
 
 
DOI no: 10.1038/emboj.2008.125 EMBO J 27:1995-2005 (2008)
PubMed id: 18596699  
 
 
Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II.
B.Stieglitz, C.Bee, D.Schwarz, O.Yildiz, A.Moshnikova, A.Khokhlatchev, C.Herrmann.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20949621 L.Gremer, T.Merbitz-Zahradnik, R.Dvorsky, I.C.Cirstea, C.P.Kratz, M.Zenker, A.Wittinghofer, and M.R.Ahmadian (2011).
Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders.
  Hum Mutat, 32, 33-43.  
20339001 C.Bee, A.Moshnikova, C.D.Mellor, J.E.Molloy, Y.Koryakina, B.Stieglitz, A.Khokhlatchev, and C.Herrmann (2010).
Growth and tumor suppressor NORE1A is a regulatory node between Ras signaling and microtubule nucleation.
  J Biol Chem, 285, 16258-16266.  
19995790 L.Gremer, A.De Luca, T.Merbitz-Zahradnik, B.Dallapiccola, S.Morlot, M.Tartaglia, K.Kutsche, M.R.Ahmadian, and G.Rosenberger (2010).
Duplication of Glu37 in the switch I region of HRAS impairs effector/GAP binding and underlies Costello syndrome by promoting enhanced growth factor-dependent MAPK and AKT activation.
  Hum Mol Genet, 19, 790-802.  
20685651 S.Karassek, C.Berghaus, M.Schwarten, C.G.Goemans, N.Ohse, G.Kock, K.Jockers, S.Neumann, S.Gottfried, C.Herrmann, R.Heumann, and R.Stoll (2010).
Ras homolog enriched in brain (Rheb) enhances apoptotic signaling.
  J Biol Chem, 285, 33979-33991.
PDB code: 2l0x
20025613 V.Sherwood, A.Recino, A.Jeffries, A.Ward, and A.D.Chalmers (2010).
The N-terminal RASSF family: a new group of Ras-association-domain-containing proteins, with emerging links to cancer formation.
  Biochem J, 425, 303-311.  
19776012 C.Kiel, D.Filchtinski, M.Spoerner, G.Schreiber, H.R.Kalbitzer, and C.Herrmann (2009).
Improved binding of raf to Ras.GDP is correlated with biological activity.
  J Biol Chem, 284, 31893-31902.  
19091744 J.Avruch, R.Xavier, N.Bardeesy, X.F.Zhang, M.Praskova, D.Zhou, and F.Xia (2009).
Rassf family of tumor suppressor polypeptides.
  J Biol Chem, 284, 11001-11005.  
19651783 M.M.Edreira, S.Li, D.Hochbaum, S.Wong, A.A.Gorfe, F.Ribeiro-Neto, V.L.Woods, and D.L.Altschuler (2009).
Phosphorylation-induced conformational changes in Rap1b: allosteric effects on switch domains and effector loop.
  J Biol Chem, 284, 27480-27486.  
19098985 S.Kuznetsov, and A.V.Khokhlatchev (2008).
The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis.
  PLoS ONE, 3, e3997.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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