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PDBsum entry 2fu5
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protein ligands metals Protein-protein interface(s) links
Signaling protein PDB id
2fu5

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
107 a.a. *
146 a.a. *
157 a.a. *
Ligands
BME ×2
Metals
_ZN ×2
Waters ×301
* Residue conservation analysis
PDB id:
2fu5
Name: Signaling protein
Title: Structure of rab8 in complex with mss4
Structure: Guanine nucleotide exchange factor mss4. Chain: a, b. Fragment: residues 11-123. Synonym: rab-interacting factor, mss4. Engineered: yes. Ras-related protein rab-8a. Chain: c, d. Fragment: residues 1-183. Synonym: oncogenE C-mel, rab8.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: rabif, mss4, rasgrf3. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. House mouse. Organism_taxid: 10090.
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.200     R-free:   0.252
Authors: A.Itzen,O.Pylypenko,R.S.Goody,A.Rak
Key ref:
A.Itzen et al. (2006). Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4. EMBO J, 25, 1445-1455. PubMed id: 16541104 DOI: 10.1038/sj.emboj.7601044
Date:
26-Jan-06     Release date:   04-Apr-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P47224  (MSS4_HUMAN) -  Guanine nucleotide exchange factor MSS4 from Homo sapiens
Seq:
Struc: 		123 a.a.
107 a.a.*
Protein chain
Pfam   ArchSchema ?
P55258  (RAB8A_MOUSE) -  Ras-related protein Rab-8A from Mus musculus
Seq:
Struc: 		207 a.a.
146 a.a.*
Protein chain
Pfam   ArchSchema ?
P55258  (RAB8A_MOUSE) -  Ras-related protein Rab-8A from Mus musculus
Seq:
Struc: 		207 a.a.
157 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 2: Chains A, B: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 3: Chains C, D: E.C.3.6.5.2  - small monomeric GTPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: GTP + H2O = GDP + phosphate + H+
GTP
 + H2O
 = GDP
 + phosphate
 + H(+)
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/sj.emboj.7601044 EMBO J 25:1445-1455 (2006)
PubMed id: 16541104  
 
 
Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4.
A.Itzen, O.Pylypenko, R.S.Goody, K.Alexandrov, A.Rak.
 
  ABSTRACT  
 
Rab GTPases function as essential regulators of vesicle transport in eukaryotic cells. MSS4 was shown to stimulate nucleotide exchange on Rab proteins associated with the exocytic pathway and to have nucleotide-free-Rab chaperone activity. A detailed kinetic analysis of MSS4 interaction with Rab8 showed that MSS4 is a relatively slow exchange factor that forms a long-lived nucleotide-free complex with RabGTPase. In contrast to other characterized exchange factor-GTPase complexes, MSS4:Rab8 complex binds GTP faster than GDP, but still ca. 3 orders of magnitude more slowly than comparable complexes. The crystal structure of the nucleotide-free MSS4:Rab8 complex revealed that MSS4 binds to the Switch I and interswitch regions of Rab8, forming an intermolecular beta-sheet. Complex formation results in dramatic structural changes of the Rab8 molecule, leading to unfolding of the nucleotide-binding site and surrounding structural elements, facilitating nucleotide release and slowing its rebinding. Coupling of nucleotide exchange activity to a cycle of GTPase unfolding and refolding represents a novel nucleotide exchange mechanism.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 Ribbon representation of the MSS4:Rab8 complex structure. The Rab8 molecule is shown in orange, MSS4 in green, and the MSS4-bound Zn^2+ ion as a gray ball. Protein regions missing in the final complex model are shown as dashed red lines. Protein termini and secondary structure elements are labeled. 		Figure 5.
Figure 5 The MSS4:Rab8 complex interface. Contacting secondary structure elements are labeled. Interacting amino-acid residues are shown in stick representation and labeled. Hydrogen bonds are shown as blue dashed lines. (A) Shared between MSS4 and Rab8 -sheet. The cluster of hydrophobic residues on the convex joint -sheet surface involving MSS4 3[10]A helix residues is shown. (B) Hydrogen-bonding network of the MSS4:Rab8. (C) The R8 SI hydrophobic surface harbored by MSS4 hydrophobic concave surface.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 1445-1455) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21194374 V.Wixler, L.Wixler, A.Altenfeld, S.Ludwig, R.S.Goody, and A.Itzen (2011).
Identification and characterisation of novel Mss4-binding Rab GTPases.
  Biol Chem, 392, 239-248.  
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
  Antioxid Redox Signal, 12, 53-91.  
20176951 Y.Zhu, L.Hu, Y.Zhou, Q.Yao, L.Liu, and F.Shao (2010).
Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA.
  Proc Natl Acad Sci U S A, 107, 4699-4704.
PDB codes: 3l0i 3l0m
19361519 H.F.Chin, Y.Cai, S.Menon, S.Ferro-Novick, K.M.Reinisch, and E.M.De La Cruz (2009).
Kinetic analysis of the guanine nucleotide exchange activity of TRAPP, a multimeric Ypt1p exchange factor.
  J Mol Biol, 389, 275-288.  
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.  
20064470 S.Schoebel, L.K.Oesterlin, W.Blankenfeldt, R.S.Goody, and A.Itzen (2009).
RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity.
  Mol Cell, 36, 1060-1072.
PDB codes: 3jz9 3jza
19670212 T.Cierpicki, J.Bielnicki, M.Zheng, J.Gruszczyk, M.Kasterka, M.Petoukhov, A.Zhang, E.J.Fernandez, D.I.Svergun, U.Derewenda, J.H.Bushweller, and Z.S.Derewenda (2009).
The solution structure and dynamics of the DH-PH module of PDZRhoGEF in isolation and in complex with nucleotide-free RhoA.
  Protein Sci, 18, 2067-2079.  
19570981 X.Dong, B.Yang, Y.Li, C.Zhong, and J.Ding (2009).
Molecular basis of the acceleration of the GDP-GTP exchange of human ras homolog enriched in brain by human translationally controlled tumor protein.
  J Biol Chem, 284, 23754-23764.
PDB code: 3ebm
18765796 E.M.Puchner, A.Alexandrovich, A.L.Kho, U.Hensen, L.V.Schäfer, B.Brandmeier, F.Gräter, H.Grubmüller, H.E.Gaub, and M.Gautel (2008).
Mechanoenzymatics of titin kinase.
  Proc Natl Acad Sci U S A, 105, 13385-13390.  
18243112 S.Cui, K.Eisenächer, A.Kirchhofer, K.Brzózka, A.Lammens, K.Lammens, T.Fujita, K.K.Conzelmann, A.Krug, and K.P.Hopfner (2008).
The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I.
  Mol Cell, 29, 169-179.
PDB codes: 2qfb 2qfd
19026641 S.H.Lee, K.Baek, and R.Dominguez (2008).
Large nucleotide-dependent conformational change in Rab28.
  FEBS Lett, 582, 4107-4111.
PDB code: 3e5h
18638444 S.L.Schwartz, M.Tessema, T.Buranda, O.Pylypenko, A.Rak, P.C.Simons, Z.Surviladze, L.A.Sklar, and A.Wandinger-Ness (2008).
Flow cytometry for real-time measurement of guanine nucleotide binding and exchange by Ras-like GTPases.
  Anal Biochem, 381, 258-266.  
17450153 A.Delprato, and D.G.Lambright (2007).
Structural basis for Rab GTPase activation by VPS9 domain exchange factors.
  Nat Struct Mol Biol, 14, 406-412.
PDB code: 2ot3
17213877 B.Kintses, M.Gyimesi, D.S.Pearson, M.A.Geeves, W.Zeng, C.R.Bagshaw, and A.Málnási-Csizmadia (2007).
Reversible movement of switch 1 loop of myosin determines actin interaction.
  EMBO J, 26, 265-274.  
17121405 C.F.Becker, Y.Marsac, P.Hazarika, J.Moser, R.S.Goody, and C.M.Niemeyer (2007).
Functional immobilization of the small GTPase Rab6A on DNA-Gold nanoparticles by using a site-specifically attached poly(ethylene glycol) linker and thiol place-exchange reaction.
  Chembiochem, 8, 32-36.  
17218277 C.Thomas, I.Fricke, A.Scrima, A.Berken, and A.Wittinghofer (2007).
Structural evidence for a common intermediate in small G protein-GEF reactions.
  Mol Cell, 25, 141-149.
PDB codes: 2ntx 2nty
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
17540168 J.L.Bos, H.Rehmann, and A.Wittinghofer (2007).
GEFs and GAPs: critical elements in the control of small G proteins.
  Cell, 129, 865-877.  
17582168 L.M.Chavas, S.Torii, H.Kamikubo, M.Kawasaki, K.Ihara, R.Kato, M.Kataoka, T.Izumi, and S.Wakatsuki (2007).
Structure of the small GTPase Rab27b shows an unexpected swapped dimer.
  Acta Crystallogr D Biol Crystallogr, 63, 769-779.
PDB codes: 2iey 2iez 2if0
17879235 T.Uno, T.Nakada, S.Okamaoto, M.Nakamura, M.Matsubara, H.Imaishi, H.Yamagata, K.Kanamaru, and M.Takagi (2007).
Determination of phosphorylated amino acid residues of Rab8 from Bombyx mori.
  Arch Insect Biochem Physiol, 66, 89-97.  
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
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.

 

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