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PDBsum entry 1aje

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protein links
G-protein PDB id
1aje
Jmol
Contents
Protein chain
194 a.a. *
* Residue conservation analysis
PDB id:
1aje
Name: G-protein
Title: Cdc42 from human, nmr, 20 structures
Structure: Cdc42hs. Chain: a. Engineered: yes. Other_details: seven non-native amino acids remain at the n-terminus after cleavage of the fusion protein
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Organ: placenta. Cellular_location: membranes and golgi. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: J.L.Feltham,V.Dotsch,S.Raza,D.Manor,R.A.Cerione, M.J.Sutcliffe,G.Wagner,R.E.Oswald
Key ref:
J.L.Feltham et al. (1997). Definition of the switch surface in the solution structure of Cdc42Hs. Biochemistry, 36, 8755-8766. PubMed id: 9220962 DOI: 10.1021/bi970694x
Date:
02-May-97     Release date:   12-Nov-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P60953  (CDC42_HUMAN) -  Cell division control protein 42 homolog
Seq:
Struc:
191 a.a.
194 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   24 terms 
  Biological process     cardiac conduction system development   70 terms 
  Biochemical function     nucleotide binding     10 terms  

 

 
DOI no: 10.1021/bi970694x Biochemistry 36:8755-8766 (1997)
PubMed id: 9220962  
 
 
Definition of the switch surface in the solution structure of Cdc42Hs.
J.L.Feltham, V.Dötsch, S.Raza, D.Manor, R.A.Cerione, M.J.Sutcliffe, G.Wagner, R.E.Oswald.
 
  ABSTRACT  
 
Proteins of the rho subfamily of ras GTPases have been shown to be crucial components of pathways leading to cell growth and the establishment of cell polarity and mobility. Presented here is the solution structure of one such protein, Cdc42Hs, which provides insight into the structural basis for specificity of interactions between this protein and its effector and regulatory proteins. Standard heteronuclear NMR methods were used to assign the protein, and approximately 2100 distance and dihedral angle constraints were used to calculate a set of 20 structures using a combination of distance geometry and simulated annealing refinement. These structures show overall similarity to those of other GTP-binding proteins, with some exceptions. The regions corresponding to switch I and switch II in H-ras are disordered, and no evidence was found for an alpha-helix in switch II. The 13-residue insertion, which is only present in rho-subtype proteins and has been shown to be an important mediator of binding of regulatory and target proteins, forms a compact structure containing a short helix lying adjacent to the beta4-alpha3 loop. The insert forms one edge of a "switch surface" and, unexpectedly, does not change conformation upon activation of the protein by the exchange of GTP analogs for GDP. These studies indicate the insert region forms a stable invariant "footrest" for docking of regulatory and effector proteins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20649471 J.Heo (2011).
Redox control of GTPases: from molecular mechanisms to functional significance in health and disease.
  Antioxid Redox Signal, 14, 689-724.  
19387844 Y.Kobashigawa, H.Kumeta, D.Kanoh, and F.Inagaki (2009).
The NMR structure of the TC10- and Cdc42-interacting domain of CIP4.
  J Biomol NMR, 44, 113-118.
PDB code: 2ke4
17984089 D.Owen, L.J.Campbell, K.Littlefield, K.A.Evetts, Z.Li, D.B.Sacks, P.N.Lowe, and H.R.Mott (2008).
The IQGAP1-Rac1 and IQGAP1-Cdc42 interactions: interfaces differ between the complexes.
  J Biol Chem, 283, 1692-1704.  
18348980 M.J.Phillips, G.Calero, B.Chan, S.Ramachandran, and R.A.Cerione (2008).
Effector proteins exert an important influence on the signaling-active state of the small GTPase Cdc42.
  J Biol Chem, 283, 14153-14164.
PDB code: 2qrz
18006505 R.Modha, L.J.Campbell, D.Nietlispach, H.R.Buhecha, D.Owen, and H.R.Mott (2008).
The Rac1 polybasic region is required for interaction with its effector PRK1.
  J Biol Chem, 283, 1492-1500.
PDB code: 2rmk
17004322 B.P.Somesh, C.Neffgen, M.Iijima, P.Devreotes, and F.Rivero (2006).
Dictyostelium RacH regulates endocytic vesicular trafficking and is required for localization of vacuolin.
  Traffic, 7, 1194-1212.  
16950926 B.P.Somesh, G.Vlahou, M.Iijima, R.H.Insall, P.Devreotes, and F.Rivero (2006).
RacG regulates morphology, phagocytosis, and chemotaxis.
  Eukaryot Cell, 5, 1648-1663.  
16980357 M.Li, J.Liu, X.Ran, M.Fang, J.Shi, H.Qin, J.M.Goh, and J.Song (2006).
Resurrecting abandoned proteins with pure water: CD and NMR studies of protein fragments solubilized in salt-free water.
  Biophys J, 91, 4201-4209.  
17053066 N.Van Eps, W.M.Oldham, H.E.Hamm, and W.L.Hubbell (2006).
Structural and dynamical changes in an alpha-subunit of a heterotrimeric G protein along the activation pathway.
  Proc Natl Acad Sci U S A, 103, 16194-16199.  
16489751 P.D.Adams, and R.E.Oswald (2006).
Solution structure of an oncogenic mutant of Cdc42Hs.
  Biochemistry, 45, 2577-2583.
PDB code: 2ase
15921909 C.DerMardirossian, and G.M.Bokoch (2005).
GDIs: central regulatory molecules in Rho GTPase activation.
  Trends Cell Biol, 15, 356-363.  
15994296 J.Heo, and S.L.Campbell (2005).
Mechanism of redox-mediated guanine nucleotide exchange on redox-active Rho GTPases.
  J Biol Chem, 280, 31003-31010.  
15653425 E.J.Helmreich (2004).
Structural flexibility of small GTPases. Can it explain their functional versatility?
  Biol Chem, 385, 1121-1136.  
12409291 M.Endo, M.Shirouzu, and S.Yokoyama (2003).
The Cdc42 binding and scaffolding activities of the fission yeast adaptor protein Scd2.
  J Biol Chem, 278, 843-852.  
11900529 R.Thapar, A.E.Karnoub, and S.L.Campbell (2002).
Structural and biophysical insights into the role of the insert region in Rac1 function.
  Biochemistry, 41, 3875-3883.  
11283263 A.E.Karnoub, C.J.Der, and S.L.Campbell (2001).
The insert region of Rac1 is essential for membrane ruffling but not cellular transformation.
  Mol Cell Biol, 21, 2847-2857.  
11294626 A.P.Loh, N.Pawley, L.K.Nicholson, and R.E.Oswald (2001).
An increase in side chain entropy facilitates effector binding: NMR characterization of the side chain methyl group dynamics in Cdc42Hs.
  Biochemistry, 40, 4590-4600.  
11113198 H.U.Mösch, T.Köhler, and G.H.Braus (2001).
Different domains of the essential GTPase Cdc42p required for growth and development of Saccharomyces cerevisiae.
  Mol Cell Biol, 21, 235-248.  
11463812 H.Zong, K.Kaibuchi, and L.A.Quilliam (2001).
The insert region of RhoA is essential for Rho kinase activation and cellular transformation.
  Mol Cell Biol, 21, 5287-5298.  
11706050 J.E.Adamo, J.J.Moskow, A.S.Gladfelter, D.Viterbo, D.J.Lew, and P.J.Brennwald (2001).
Yeast Cdc42 functions at a late step in exocytosis, specifically during polarized growth of the emerging bud.
  J Cell Biol, 155, 581-592.  
11738594 K.D.Corbett, and T.Alber (2001).
The many faces of Ras: recognition of small GTP-binding proteins.
  Trends Biochem Sci, 26, 710-716.  
10799524 B.C.Low, K.T.Seow, and G.R.Guy (2000).
Evidence for a novel Cdc42GAP domain at the carboxyl terminus of BNIP-2.
  J Biol Chem, 275, 14415-14422.  
10747784 D.Gizachew, W.Guo, K.K.Chohan, M.J.Sutcliffe, and R.E.Oswald (2000).
Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase.
  Biochemistry, 39, 3963-3971.
PDB code: 1ees
10684602 D.Owen, H.R.Mott, E.D.Laue, and P.N.Lowe (2000).
Residues in Cdc42 that specify binding to individual CRIB effector proteins.
  Biochemistry, 39, 1243-1250.  
  10637312 K.G.Kozminski, A.J.Chen, A.A.Rodal, and D.G.Drubin (2000).
Functions and functional domains of the GTPase Cdc42p.
  Mol Biol Cell, 11, 339-354.  
  10066831 D.I.Johnson (1999).
Cdc42: An essential Rho-type GTPase controlling eukaryotic cell polarity.
  Microbiol Mol Biol Rev, 63, 54.  
9988689 H.Zong, N.Raman, L.A.Mickelson-Young, S.J.Atkinson, and L.A.Quilliam (1999).
Loop 6 of RhoA confers specificity for effector binding, stress fiber formation, and cellular transformation.
  J Biol Chem, 274, 4551-4560.  
10489445 K.Longenecker, P.Read, U.Derewenda, Z.Dauter, X.Liu, S.Garrard, L.Walker, A.V.Somlyo, R.K.Nakamoto, A.P.Somlyo, and Z.S.Derewenda (1999).
How RhoGDI binds Rho.
  Acta Crystallogr D Biol Crystallogr, 55, 1503-1515.
PDB code: 1cc0
  10211824 M.G.Rudolph, A.Wittinghofer, and I.R.Vetter (1999).
Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different nucleotide states in one crystal.
  Protein Sci, 8, 778-787.
PDB code: 1a4r
10514434 R.Li, B.Debreceni, B.Jia, Y.Gao, G.Tigyi, and Y.Zheng (1999).
Localization of the PAK1-, WASP-, and IQGAP1-specifying regions of Cdc42.
  J Biol Chem, 274, 29648-29654.  
10438546 R.Lin, R.A.Cerione, and D.Manor (1999).
Specific contributions of the small GTPases Rho, Rac, and Cdc42 to Dbl transformation.
  J Biol Chem, 274, 23633-23641.  
10625453 T.Nomanbhoy, and R.A.Cerione (1999).
Fluorescence assays of Cdc42 interactions with target/effector proteins.
  Biochemistry, 38, 15878-15884.  
10320322 W.K.Stevens, W.Vranken, N.Goudreau, H.Xiang, P.Xu, and F.Ni (1999).
Conformation of a Cdc42/Rac interactive binding peptide in complex with Cdc42 and analysis of the binding interface.
  Biochemistry, 38, 5968-5975.  
9748241 B.Zhang, and Y.Zheng (1998).
Negative regulation of Rho family GTPases Cdc42 and Rac2 by homodimer formation.
  J Biol Chem, 273, 25728-25733.  
9846874 N.Nassar, G.R.Hoffman, D.Manor, J.C.Clardy, and R.A.Cerione (1998).
Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP.
  Nat Struct Biol, 5, 1047-1052.
PDB codes: 1grn 2ngr
9631293 S.J.Gamblin, and S.J.Smerdon (1998).
GTPase-activating proteins and their complexes.
  Curr Opin Struct Biol, 8, 195-201.  
9760238 W.Guo, M.J.Sutcliffe, R.A.Cerione, and R.E.Oswald (1998).
Identification of the binding surface on Cdc42Hs for p21-activated kinase.
  Biochemistry, 37, 14030-14037.  
9642217 W.J.Wu, R.Lin, R.A.Cerione, and D.Manor (1998).
Transformation activity of Cdc42 requires a region unique to Rho-related proteins.
  J Biol Chem, 273, 16655-16658.  
9434896 M.Geyer, and A.Wittinghofer (1997).
GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins.
  Curr Opin Struct Biol, 7, 786-792.  
9368762 R.Lin, S.Bagrodia, R.Cerione, and D.Manor (1997).
A novel Cdc42Hs mutant induces cellular transformation.
  Curr Biol, 7, 794-797.  
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.