spacer
spacer

PDBsum entry 1g16

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Signaling protein,endocytosis/exocytosis PDB id
1g16
Jmol
Contents
Protein chains
159 a.a. *
167 a.a. *
Ligands
GDP ×4
Metals
_CO ×8
Waters ×328
* Residue conservation analysis
PDB id:
1g16
Name: Signaling protein,endocytosis/exocytosis
Title: Crystal structure of sec4-gdp
Structure: Ras-related protein sec4. Chain: a, b, c, d. Fragment: residues 18-187. Synonym: gtp-binding protein sec4. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.276     R-free:   0.296
Authors: C.Stroupe,A.T.Brunger
Key ref: C.Stroupe and A.T.Brunger (2000). Crystal structures of a Rab protein in its inactive and active conformations. J Mol Biol, 304, 585-598. PubMed id: 11099382 DOI: 10.1006/jmbi.2000.4236
Date:
10-Oct-00     Release date:   11-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P07560  (SEC4_YEAST) -  Ras-related protein SEC4
Seq:
Struc:
215 a.a.
159 a.a.*
Protein chains
Pfam   ArchSchema ?
P07560  (SEC4_YEAST) -  Ras-related protein SEC4
Seq:
Struc:
215 a.a.
167 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein transport   2 terms 
  Biochemical function     GTP binding     1 term  

 

 
DOI no: 10.1006/jmbi.2000.4236 J Mol Biol 304:585-598 (2000)
PubMed id: 11099382  
 
 
Crystal structures of a Rab protein in its inactive and active conformations.
C.Stroupe, A.T.Brunger.
 
  ABSTRACT  
 
We have determined crystal structures of Sec4, a member of the Rab family in the G protein superfamily, in two states: bound to GDP, and to a non-hydrolyzable GTP analog, guanosine-5'-(beta, gamma)-imidotriphosphate (GppNHp). This represents the first structure of a Rab protein bound to GDP. Sec4 in both states grossly resembles other G proteins bound to GDP and GppNHp. In Sec4-GppNHp, structural features common to active Rab proteins are observed. In Sec4-GDP, the switch I region is highly disordered and displaced relative to the switch I region of Ras-GDP. In two of the four molecules of Sec4-GDP in the asymmetric unit of the Sec4-GDP crystals, the switch II region adopts a conformation similar to that seen in the structure of the small G protein Ran bound to GDP. This allows residues threonine 76, glutamate 80, and arginine 81 of Sec4 to make contacts with other conserved residues and water molecules important for nucleotide binding. In the other two molecules in the asymmetric unit, these interactions do not take place. This structural variability in both the switch I and switch II regions of GDP-bound Sec4 provides a possible explanation for the high off-rate of GDP bound to Sec4, and suggests a mechanism for regulation of the GTPase cycle of Rab proteins by GDI proteins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19265520 A.F.Neuwald (2009).
The glycine brace: a component of Rab, Rho, and Ran GTPases associated with hinge regions of guanine- and phosphate-binding loops.
  BMC Struct Biol, 9, 11.  
19427324 A.F.Neuwald (2009).
The charge-dipole pocket: a defining feature of signaling pathway GTPase on/off switches.
  J Mol Biol, 390, 142-153.  
19522756 M.T.Lee, A.Mishra, and D.G.Lambright (2009).
Structural mechanisms for regulation of membrane traffic by rab GTPases.
  Traffic, 10, 1377-1389.  
18243103 A.S.Burguete, T.D.Fenn, A.T.Brunger, and S.R.Pfeffer (2008).
Rab and Arl GTPase family members cooperate in the localization of the golgin GCC185.
  Cell, 132, 286-298.
PDB code: 3bbp
17952054 A.Ingmundson, A.Delprato, D.G.Lambright, and C.R.Roy (2007).
Legionella pneumophila proteins that regulate Rab1 membrane cycling.
  Nature, 450, 365-369.  
17289591 G.Dong, M.Medkova, P.Novick, and K.M.Reinisch (2007).
A catalytic coiled coil: structural insights into the activation of the Rab GTPase Sec4p by Sec2p.
  Mol Cell, 25, 455-462.
PDB code: 2ocy
17292842 Y.Sato, R.Shirakawa, H.Horiuchi, N.Dohmae, S.Fukai, and O.Nureki (2007).
Asymmetric coiled-coil structure with Guanine nucleotide exchange activity.
  Structure, 15, 245-252.
PDB code: 2e7s
17488829 Y.Sato, S.Fukai, R.Ishitani, and O.Nureki (2007).
Crystal structure of the Sec4p.Sec2p complex in the nucleotide exchanging intermediate state.
  Proc Natl Acad Sci U S A, 104, 8305-8310.
PDB code: 2eqb
16541104 A.Itzen, O.Pylypenko, R.S.Goody, K.Alexandrov, and A.Rak (2006).
Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4.
  EMBO J, 25, 1445-1455.
PDB code: 2fu5
16790928 I.Garcia-Saez, S.Tcherniuk, and F.Kozielski (2006).
The structure of human neuronal Rab6B in the active and inactive form.
  Acta Crystallogr D Biol Crystallogr, 62, 725-733.
PDB codes: 2fe4 2ffq
16395697 J.M.Cheng, M.Ding, A.Aribi, P.Shah, and K.Rao (2006).
Loss of RAB25 expression in breast cancer.
  Int J Cancer, 118, 2957-2964.  
17031879 L.Brunsveld, J.Kuhlmann, K.Alexandrov, A.Wittinghofer, R.S.Goody, and H.Waldmann (2006).
Lipidated ras and rab peptides and proteins--synthesis, structure, and function.
  Angew Chem Int Ed Engl, 45, 6622-6646.  
15785799 A.Watzke, L.Brunsveld, T.Durek, K.Alexandrov, A.Rak, R.S.Goody, and H.Waldmann (2005).
Chemical biology of protein lipidation: semi-synthesis and structure elucidation of prenylated RabGTPases.
  Org Biomol Chem, 3, 1157-1164.  
15746102 S.R.Pfeffer (2005).
Structural clues to Rab GTPase functional diversity.
  J Biol Chem, 280, 15485-15488.  
14978301 C.Blouin, D.Butt, and A.J.Roger (2004).
Rapid evolution in conformational space: a study of loop regions in a ubiquitous GTP binding domain.
  Protein Sci, 13, 608-616.  
15378032 G.Zhu, P.Zhai, J.Liu, S.Terzyan, G.Li, and X.C.Zhang (2004).
Structural basis of Rab5-Rabaptin5 interaction in endocytosis.
  Nat Struct Mol Biol, 11, 975-983.
PDB codes: 1tu3 1tu4
15263003 L.Chen, E.DiGiammarino, X.E.Zhou, Y.Wang, D.Toh, T.W.Hodge, and E.J.Meehan (2004).
High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target.
  J Biol Chem, 279, 40204-40208.
PDB code: 1wms
14699104 S.Pasqualato, F.Senic-Matuglia, L.Renault, B.Goud, J.Salamero, and J.Cherfils (2004).
The structural GDP/GTP cycle of Rab11 reveals a novel interface involved in the dynamics of recycling endosomes.
  J Biol Chem, 279, 11480-11488.
PDB codes: 1oiv 1oiw
15520808 S.Pfeffer, and D.Aivazian (2004).
Targeting Rab GTPases to distinct membrane compartments.
  Nat Rev Mol Cell Biol, 5, 886-896.  
12433916 G.Zhu, J.Liu, S.Terzyan, P.Zhai, G.Li, and X.C.Zhang (2003).
High resolution crystal structures of human Rab5a and five mutants with substitutions in the catalytically important phosphate-binding loop.
  J Biol Chem, 278, 2452-2460.
PDB codes: 1n6h 1n6i 1n6k 1n6l 1n6n 1n6o 1n6p 1n6r
11937061 A.T.Constantinescu, A.Rak, K.Alexandrov, H.Esters, R.S.Goody, and A.J.Scheidig (2002).
Rab-subfamily-specific regions of Ypt7p are structurally different from other RabGTPases.
  Structure, 10, 569-579.
PDB codes: 1ky2 1ky3
12105226 D.J.Strick, D.M.Francescutti, Y.Zhao, and L.A.Elferink (2002).
Mammalian suppressor of Sec4 modulates the inhibitory effect of Rab15 during early endocytosis.
  J Biol Chem, 277, 32722-32729.  
12192047 D.Riedel, W.Antonin, R.Fernandez-Chacon, G.Alvarez de Toledo, T.Jo, M.Geppert, J.A.Valentijn, K.Valentijn, J.D.Jamieson, T.C.Südhof, and R.Jahn (2002).
Rab3D is not required for exocrine exocytosis but for maintenance of normally sized secretory granules.
  Mol Cell Biol, 22, 6487-6497.  
12048186 M.Geymonat, A.Spanos, S.J.Smith, E.Wheatley, K.Rittinger, L.H.Johnston, and S.G.Sedgwick (2002).
Control of mitotic exit in budding yeast. In vitro regulation of Tem1 GTPase by Bub2 and Bfa1.
  J Biol Chem, 277, 28439-28445.  
11784320 X.Bao, A.E.Faris, E.K.Jang, and R.J.Haslam (2002).
Molecular cloning, bacterial expression and properties of Rab31 and Rab32.
  Eur J Biochem, 269, 259-271.  
11297924 A.T.Brunger (2001).
Structural insights into the molecular mechanism of calcium-dependent vesicle-membrane fusion.
  Curr Opin Struct Biol, 11, 163-173.  
  11387043 H.Stenmark, and V.M.Olkkonen (2001).
The Rab GTPase family.
  Genome Biol, 2, REVIEWS3007.  
11454458 N.Segev (2001).
Ypt and Rab GTPases: insight into functions through novel interactions.
  Curr Opin Cell Biol, 13, 500-511.  
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.