PDBsum entry 2fju

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protein ligands metals Protein-protein interface(s) links
Signaling protein,apoptosis/hydrolase PDB id
Protein chains
177 a.a. *
696 a.a. *
Waters ×486
* Residue conservation analysis
PDB id:
Name: Signaling protein,apoptosis/hydrolase
Title: Activated rac1 bound to its effector phospholipasE C beta 2
Structure: Ras-related c3 botulinum toxin substrate 1. Chain: a. Fragment: residues 1-189. Synonym: p21-rac1. Ras-like protein tc25. Engineered: yes. 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta 2. Chain: b. Fragment: residues 1-799.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: rac1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: plcb2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Dimer (from PQS)
2.20Å     R-factor:   0.208     R-free:   0.226
Authors: M.R.Jezyk,J.T.Snyder,T.K.Harden,J.Sondek
Key ref:
M.R.Jezyk et al. (2006). Crystal structure of Rac1 bound to its effector phospholipase C-beta2. Nat Struct Mol Biol, 13, 1135-1140. PubMed id: 17115053 DOI: 10.1038/nsmb1175
03-Jan-06     Release date:   21-Nov-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P63000  (RAC1_HUMAN) -  Ras-related C3 botulinum toxin substrate 1
192 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
Q00722  (PLCB2_HUMAN) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2
1185 a.a.
696 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain B: E.C.  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

myo-Inositol Phosphate Metabolism
      Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
+ H(2)O
= 1D-myo-inositol 1,4,5-trisphosphate
+ diacylglycerol
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   19 terms 
  Biological process     epithelial cell morphogenesis   76 terms 
  Biochemical function     nucleotide binding     14 terms  


DOI no: 10.1038/nsmb1175 Nat Struct Mol Biol 13:1135-1140 (2006)
PubMed id: 17115053  
Crystal structure of Rac1 bound to its effector phospholipase C-beta2.
M.R.Jezyk, J.T.Snyder, S.Gershberg, D.K.Worthylake, T.K.Harden, J.Sondek.
Although diverse signaling cascades require the coordinated regulation of heterotrimeric G proteins and small GTPases, these connections remain poorly understood. We present the crystal structure of the GTPase Rac1 bound to phospholipase C-beta2 (PLC-beta2), a classic effector of heterotrimeric G proteins. Rac1 engages the pleckstrin-homology (PH) domain of PLC-beta2 to optimize its orientation for substrate membranes. Gbetagamma also engages the PH domain to activate PLC-beta2, and these two activation events are compatible, leading to additive stimulation of phospholipase activity. In contrast to PLC-delta, the PH domain of PLC-beta2 cannot bind phosphoinositides, eliminating this mode of regulation. The structure of the Rac1-PLC-beta2 complex reveals determinants that dictate selectivity of PLC-beta isozymes for Rac GTPases over other Rho-family GTPases, and substitutions within PLC-beta2 abrogate its stimulation by Rac1 but not by Gbetagamma, allowing for functional dissection of this integral signaling node.
  Selected figure(s)  
Figure 1.
Figure 1. Structure of activated Rac1 in complex with PLC- 2. (a) Domain architecture of PLC- 2. PLC- 2 has the conserved core of all PLC enzymes, which includes an N-terminal PH domain followed by four EF hands, a catalytic TIM barrel and a C2 domain. PLC- isozymes elaborate this core with a C-terminal coiled-coil domain (CT), which mediates homodimerization and phospholipase stimulation by G q. This region, which is not necessary for Rac activation, was removed to facilitate crystallization, by truncation of PLC- 2 at residue 799 (arrow). (b) Ribbon diagram of overall structure of Rac1 bound to the conserved core of PLC- 2, as viewed from below the plane of the membrane. Activated Rac1, bound to the nonhydrolyzable GTP analog GTP- S (cyan), engages solely the PH domain of PLC- 2. Switch regions (Sw1, Sw2) are also indicated (red). (c) View rotated about the x-axis by 90°, showing membrane-anchored orientation of the Rac1–PLC- 2 complex. The geranylgeranylated C terminus of Rac1 and the substrate of PLC- 2, PI(4,5)P[2], are modeled as sites of membrane attachment.
Figure 2.
Figure 2. Intermolecular interface of Rac1 and PLC- 2. (a) Surface representation and schematic of the PH domain of PLC- 2 (gray) engaging the switch regions of Rac1 (red). Contact residues of the PH domain are highlighted (blue). (b) Close-up view of a highlighting intermolecular contacts. Gln52 and Tyr118 of PLC- 2 form central points of the interface and are stabilized by a tight network of hydrogen bonds and -orbital interactions.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 1135-1140) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21822282 A.M.Lyon, V.M.Tesmer, V.D.Dhamsania, D.M.Thal, J.Gutierrez, S.Chowdhury, K.C.Suddala, J.K.Northup, and J.J.Tesmer (2011).
An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation.
  Nat Struct Mol Biol, 18, 999.
PDB codes: 3qr0 3qr1
21035486 J.K.Kim, S.Lim, J.Kim, S.Kim, J.H.Kim, S.H.Ryu, and P.G.Suh (2011).
Subtype-specific roles of phospholipase C-β via differential interactions with PDZ domain proteins.
  Adv Enzyme Regul, 51, 138-151.  
  21541969 K.Morgan, E.Stavrou, S.P.Leighton, N.Miller, R.Sellar, and R.P.Millar (2011).
Elevated GnRH receptor expression plus GnRH agonist treatment inhibits the growth of a subset of papillomavirus 18-immortalized human prostate cells.
  Prostate, 71, 915-928.  
20870410 T.D.Bunney, and M.Katan (2011).
PLC regulation: emerging pictures for molecular mechanisms.
  Trends Biochem Sci, 36, 88-96.  
20966218 G.L.Waldo, T.K.Ricks, S.N.Hicks, M.L.Cheever, T.Kawano, K.Tsuboi, X.Wang, C.Montell, T.Kozasa, J.Sondek, and T.K.Harden (2010).
Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex.
  Science, 330, 974-980.
PDB code: 3ohm
20062059 M.Yamashita, K.Kurokawa, Y.Sato, A.Yamagata, H.Mimura, A.Yoshikawa, K.Sato, A.Nakano, and S.Fukai (2010).
Structural basis for the Rho- and phosphoinositide-dependent localization of the exocyst subunit Sec3.
  Nat Struct Mol Biol, 17, 180-186.
PDB code: 3a58
20007712 O.Gutman, C.Walliser, T.Piechulek, P.Gierschik, and Y.I.Henis (2010).
Differential regulation of phospholipase C-beta2 activity and membrane interaction by Galphaq, Gbeta1gamma2, and Rac2.
  J Biol Chem, 285, 3905-3915.  
19864426 T.Oda, H.Hashimoto, N.Kuwabara, S.Akashi, K.Hayashi, C.Kojima, H.L.Wong, T.Kawasaki, K.Shimamoto, M.Sato, and T.Shimizu (2010).
Structure of the N-terminal regulatory domain of a plant NADPH oxidase and its functional implications.
  J Biol Chem, 285, 1435-1445.
PDB code: 3a8r
19531496 K.L.Everett, T.D.Bunney, Y.Yoon, F.Rodrigues-Lima, R.Harris, P.C.Driscoll, K.Abe, H.Fuchs, Angelis, P.Yu, W.Cho, and M.Katan (2009).
Characterization of phospholipase C gamma enzymes with gain-of-function mutations.
  J Biol Chem, 284, 23083-23093.  
19394299 T.D.Bunney, O.Opaleye, S.M.Roe, P.Vatter, R.W.Baxendale, C.Walliser, K.L.Everett, M.B.Josephs, C.Christow, F.Rodrigues-Lima, P.Gierschik, L.H.Pearl, and M.Katan (2009).
Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2.
  Mol Cell, 34, 223-233.
PDB codes: 2w2t 2w2v 2w2w 2w2x
  19033212 T.K.Harden, S.N.Hicks, and J.Sondek (2009).
Phospholipase C isozymes as effectors of Ras superfamily GTPases.
  J Lipid Res, 50, S243-S248.  
19519170 Y.Zhang, S.H.Kwon, W.K.Vogel, and T.M.Filtz (2009).
PI(3,4,5)P3 potentiates phospholipase C-beta activity.
  J Recept Signal Transduct Res, 29, 52-62.  
18488142 A.V.Smrcka (2008).
G protein betagamma subunits: central mediators of G protein-coupled receptor signaling.
  Cell Mol Life Sci, 65, 2191-2214.  
18728011 C.Walliser, M.Retlich, R.Harris, K.L.Everett, M.B.Josephs, P.Vatter, D.Esposito, P.C.Driscoll, M.Katan, P.Gierschik, and T.D.Bunney (2008).
Rac Regulates Its Effector Phospholipase C{gamma}2 through Interaction with a Split Pleckstrin Homology Domain.
  J Biol Chem, 283, 30351-30362.
PDB code: 2k2j
18923057 J.N.Rao, S.V.Liu, T.Zou, L.Liu, L.Xiao, X.Zhang, E.Bellavance, J.X.Yuan, and J.Y.Wang (2008).
Rac1 promotes intestinal epithelial restitution by increasing Ca2+ influx through interaction with phospholipase C-(gamma)1 after wounding.
  Am J Physiol Cell Physiol, 295, C1499-C1509.  
18765661 J.P.Seifert, Y.Zhou, S.N.Hicks, J.Sondek, and T.K.Harden (2008).
Dual Activation of Phospholipase C-{epsilon} by Rho and Ras GTPases.
  J Biol Chem, 283, 29690-29698.  
18787122 L.K.Jackson, P.Nawabi, C.Hentea, E.A.Roark, and K.Haldar (2008).
The Salmonella virulence protein SifA is a G protein antagonist.
  Proc Natl Acad Sci U S A, 105, 14141-14146.  
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
18691970 S.N.Hicks, M.R.Jezyk, S.Gershburg, J.P.Seifert, T.K.Harden, and J.Sondek (2008).
General and versatile autoinhibition of PLC isozymes.
  Mol Cell, 31, 383-394.
PDB code: 2zkm
18361507 Y.Zhou, J.Sondek, and T.K.Harden (2008).
Activation of human phospholipase C-eta2 by Gbetagamma.
  Biochemistry, 47, 4410-4417.  
17524618 G.Drin, and S.Scarlata (2007).
Stimulation of phospholipase Cbeta by membrane interactions, interdomain movement, and G protein binding--how many ways can you activate an enzyme?
  Cell Signal, 19, 1383-1392.  
18034889 S.G.Jackson, Y.Zhang, R.J.Haslam, and M.S.Junop (2007).
Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate.
  BMC Struct Biol, 7, 80.
PDB codes: 2i5c 2i5f
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 codes are shown on the right.