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PDBsum entry 1uad

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protein ligands metals Protein-protein interface(s) links
Endocytosis/exocytosis PDB id
1uad
Jmol
Contents
Protein chains
173 a.a. *
92 a.a. *
Ligands
GNP ×2
Metals
_MG ×2
Waters ×222
* Residue conservation analysis
PDB id:
1uad
Name: Endocytosis/exocytosis
Title: Crystal structure of the rala-gppnhp-sec5 ral-binding domain complex
Structure: Ras-related protein ral-a. Chain: a, b. Fragment: residues 9-183. Synonym: rala. Engineered: yes. Exocyst complex component sec5. Chain: c, d. Fragment: n-terminal domain, sec5 ral-binding domain. Synonym: rsec5.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Rattus norvegicus. Norway rat. Organism_taxid: 10116.
Biol. unit: Octamer (from PQS)
Resolution:
2.10Å     R-factor:   0.219     R-free:   0.254
Authors: S.Fukai,H.T.Matern,R.H.Scheller,A.T.Brunger
Key ref: S.Fukai et al. (2003). Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex. EMBO J, 22, 3267-3278. PubMed id: 12839989
Date:
09-Mar-03     Release date:   15-Jul-03    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11233  (RALA_HUMAN) -  Ras-related protein Ral-A
Seq:
Struc:
206 a.a.
173 a.a.
Protein chains
Pfam   ArchSchema ?
O54921  (EXOC2_RAT) -  Exocyst complex component 2
Seq:
Struc:
 
Seq:
Struc:
924 a.a.
92 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     signal transduction   4 terms 
  Biochemical function     GTP binding     2 terms  

 

 
EMBO J 22:3267-3278 (2003)
PubMed id: 12839989  
 
 
Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex.
S.Fukai, H.T.Matern, J.R.Jagath, R.H.Scheller, A.T.Brunger.
 
  ABSTRACT  
 
The sec6/8 complex or exocyst is an octameric protein complex that functions during cell polarization by regulating the site of exocytic vesicle docking to the plasma membrane, in concert with small GTP-binding proteins. The Sec5 subunit of the mammalian sec6/8 complex binds Ral in a GTP-dependent manner. Here we report the crystal structure of the complex between the Ral-binding domain of Sec5 and RalA bound to a non-hydrolyzable GTP analog (GppNHp) at 2.1 A resolution, providing the first structural insights into the mechanism and specificity of sec6/8 regulation. The Sec5 Ral-binding domain folds into an immunoglobulin-like beta-sandwich structure, which represents a novel fold for an effector of a GTP-binding protein. The interface between the two proteins involves a continuous antiparallel beta-sheet, similar to that found in other effector/G-protein complexes, such as Ras and Rap1A. Specific interactions unique to the RalA.Sec5 complex include Sec5 Thr11 and Arg27, and RalA Glu38, which we show are required for complex formation by isothermal titration calorimetry. Comparison of the structures of GppNHp- and GDP-bound RalA suggests a nucleotide-dependent switch mechanism for Sec5 binding.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21235523 M.Hertzog, and P.Chavrier (2011).
Cell polarity during motile processes: keeping on track with the exocyst complex.
  Biochem J, 433, 403-409.  
21516108 X.W.Chen, D.Leto, J.Xiao, J.Goss, Q.Wang, J.A.Shavit, T.Xiong, G.Yu, D.Ginsburg, D.Toomre, Z.Xu, and A.R.Saltiel (2011).
Exocyst function regulated by effector phosphorylation.
  Nat Cell Biol, 13, 580-588.  
19575650 I.M.Yu, and F.M.Hughson (2010).
Tethering factors as organizers of intracellular vesicular traffic.
  Annu Rev Cell Dev Biol, 26, 137-156.  
20139078 K.Baek, A.Knödler, S.H.Lee, X.Zhang, K.Orlando, J.Zhang, T.J.Foskett, W.Guo, and R.Dominguez (2010).
Structure-function study of the N-terminal domain of exocyst subunit Sec3.
  J Biol Chem, 285, 10424-10433.
PDB code: 3hie
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
20005108 N.Balasubramanian, J.A.Meier, D.W.Scott, A.Norambuena, M.A.White, and M.A.Schwartz (2010).
RalA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling.
  Curr Biol, 20, 75-79.  
20696399 R.B.Fenwick, L.J.Campbell, K.Rajasekar, S.Prasannan, D.Nietlispach, J.Camonis, D.Owen, and H.R.Mott (2010).
The RalB-RLIP76 complex reveals a novel mode of ral-effector interaction.
  Structure, 18, 985-995.
PDB codes: 2kwh 2kwi
19887069 E.Sztul, and V.Lupashin (2009).
Role of vesicle tethering factors in the ER-Golgi membrane traffic.
  FEBS Lett, 583, 3770-3783.  
19214222 N.J.Croteau, M.L.Furgason, D.Devos, and M.Munson (2009).
Conservation of helical bundle structure between the exocyst subunits.
  PLoS ONE, 4, e4443.  
  20161436 R.S.Kang, and H.Fölsch (2009).
An old dog learns new tricks: novel functions of the exocyst complex in polarized epithelia in animals.
  F1000 Biol Rep, 1, nihpa159599.  
19520869 R.Shirakawa, S.Fukai, M.Kawato, T.Higashi, H.Kondo, T.Ikeda, E.Nakayama, K.Okawa, O.Nureki, T.Kimura, T.Kita, and H.Horiuchi (2009).
Tuberous Sclerosis Tumor Suppressor Complex-like Complexes Act as GTPase-activating Proteins for Ral GTPases.
  J Biol Chem, 284, 21580-21588.  
18704904 D.J.Gauthier, J.A.Sobota, F.Ferraro, R.E.Mains, and C.Lazure (2008).
Flow cytometry-assisted purification and proteomic analysis of the corticotropes dense-core secretory granules.
  Proteomics, 8, 3848-3861.  
18756269 I.Cascone, R.Selimoglu, C.Ozdemir, E.Del Nery, C.Yeaman, M.White, and J.Camonis (2008).
Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs.
  EMBO J, 27, 2375-2387.  
17938170 M.Kawato, R.Shirakawa, H.Kondo, T.Higashi, T.Ikeda, K.Okawa, S.Fukai, O.Nureki, T.Kita, and H.Horiuchi (2008).
Regulation of platelet dense granule secretion by the Ral GTPase-exocyst pathway.
  J Biol Chem, 283, 166-174.  
17565980 L.F.Cavanaugh, X.Chen, B.C.Richardson, D.Ungar, I.Pelczer, J.Rizo, and F.M.Hughson (2007).
Structural analysis of conserved oligomeric Golgi complex subunit 2.
  J Biol Chem, 282, 23418-23426.
PDB code: 2jqq
17875936 S.C.Falsetti, D.A.Wang, H.Peng, D.Carrico, A.D.Cox, C.J.Der, A.D.Hamilton, and S.M.Sebti (2007).
Geranylgeranyltransferase I inhibitors target RalB to inhibit anchorage-dependent growth and induce apoptosis and RalA to inhibit anchorage-independent growth.
  Mol Cell Biol, 27, 8003-8014.  
16781882 E.M.van Dam, and P.J.Robinson (2006).
Ral: mediator of membrane trafficking.
  Int J Biochem Cell Biol, 38, 1841-1847.  
16826234 M.Munson, and P.Novick (2006).
The exocyst defrocked, a framework of rods revealed.
  Nat Struct Mol Biol, 13, 577-581.  
16177825 A.Pautsch, M.Vogelsgesang, J.Tränkle, C.Herrmann, and K.Aktories (2005).
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.
  EMBO J, 24, 3670-3680.
PDB codes: 2a78 2a9k
15955846 B.Sommer, A.Oprins, C.Rabouille, and S.Munro (2005).
The exocyst component Sec5 is present on endocytic vesicles in the oocyte of Drosophila melanogaster.
  J Cell Biol, 169, 953-963.  
16249794 G.Dong, A.H.Hutagalung, C.Fu, P.Novick, and K.M.Reinisch (2005).
The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif.
  Nat Struct Mol Biol, 12, 1094-1100.
PDB codes: 2b1e 2d2s
15953551 J.H.Camonis, and M.A.White (2005).
Ral GTPases: corrupting the exocyst in cancer cells.
  Trends Cell Biol, 15, 327-332.  
15809419 K.P.Holbourn, J.M.Sutton, H.R.Evans, C.C.Shone, and K.R.Acharya (2005).
Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase.
  Proc Natl Acad Sci U S A, 102, 5357-5362.
PDB codes: 1wca 2bov
15920473 R.Jin, J.R.Junutula, H.T.Matern, K.E.Ervin, R.H.Scheller, and A.T.Brunger (2005).
Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase.
  EMBO J, 24, 2064-2074.
PDB codes: 1zc3 1zc4
14978027 L.Wang, G.Li, and S.Sugita (2004).
RalA-exocyst interaction mediates GTP-dependent exocytosis.
  J Biol Chem, 279, 19875-19881.  
15384176 M.J.Cliff, A.Gutierrez, and J.E.Ladbury (2004).
A survey of the year 2003 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 17, 513-523.  
15199131 M.Shipitsin, and L.A.Feig (2004).
RalA but not RalB enhances polarized delivery of membrane proteins to the basolateral surface of epithelial cells.
  Mol Cell Biol, 24, 5746-5756.  
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.