PDBsum entry 1yzq

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Protein transport PDB id
Protein chain
164 a.a. *
Waters ×195
* Residue conservation analysis
PDB id:
Name: Protein transport
Title: Gppnhp-bound rab6 gtpase
Structure: Small gtp binding protein rab6 isoform. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: rab6. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.78Å     R-factor:   0.232     R-free:   0.265
Authors: S.Eathiraj,X.Pan,C.Ritacco,D.G.Lambright
Key ref:
S.Eathiraj et al. (2005). Structural basis of family-wide Rab GTPase recognition by rabenosyn-5. Nature, 436, 415-419. PubMed id: 16034420 DOI: 10.1038/nature03798
28-Feb-05     Release date:   26-Jul-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P20340  (RAB6A_HUMAN) -  Ras-related protein Rab-6A
208 a.a.
164 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   2 terms 
  Biological process     signal transduction   6 terms 
  Biochemical function     GTP binding     2 terms  


DOI no: 10.1038/nature03798 Nature 436:415-419 (2005)
PubMed id: 16034420  
Structural basis of family-wide Rab GTPase recognition by rabenosyn-5.
S.Eathiraj, X.Pan, C.Ritacco, D.G.Lambright.
Rab GTPases regulate all stages of membrane trafficking, including vesicle budding, cargo sorting, transport, tethering and fusion. In the inactive (GDP-bound) conformation, accessory factors facilitate the targeting of Rab GTPases to intracellular compartments. After nucleotide exchange to the active (GTP-bound) conformation, Rab GTPases interact with functionally diverse effectors including lipid kinases, motor proteins and tethering complexes. How effectors distinguish between homologous Rab GTPases represents an unresolved problem with respect to the specificity of vesicular trafficking. Using a structural proteomic approach, we have determined the specificity and structural basis underlying the interaction of the multivalent effector rabenosyn-5 with the Rab family. The results demonstrate that even the structurally similar effector domains in rabenosyn-5 can achieve highly selective recognition of distinct subsets of Rab GTPases exclusively through interactions with the switch and interswitch regions. The observed specificity is determined at a family-wide level by structural diversity in the active conformation, which governs the spatial disposition of critical conserved recognition determinants, and by a small number of both positive and negative sequence determinants that allow further discrimination between Rab GTPases with similar switch conformations.
  Selected figure(s)  
Figure 2.
Figure 2: Quantitative family-wide analysis of Rab GTPase -effector specificity. a, Initial screen for the interaction of 6 His (or GST) fusions of Rab GTPases with GST (or 6 His) fusions of Rbsn(440 -503) and Rbsn(728 -784). For each potential interaction, the equilibrium surface plasmon resonance signal (R[eq]) was measured at four concentrations of the 6 His Rab GTPase or 6 His Rbsn construct. b, Concentration dependence of the equilibrium surface plasmon resonance signal (R[eq]) for the binding of 6 His Rab GTPases to GST fusions of Rbsn(440 -503) and Rbsn(728 -784). Mean K[d] values and standard deviations for two to four independent experiments are tabulated on the right.
Figure 3.
Figure 3: Structural basis of Rab recognition by rabenosyn-5. a, Ribbon rendering of GTP-bound Rab4(Q67L) and Rab22(Q64L) in complex with the minimal Rab binding domains of rabenosyn-5. b, Conservation and variability in the Rab22 -Rbsn(728 -784) interface. Spheres covered by a semitransparent surface represent Rab22 (left panel) or Rbsn(728 -784) (middle panel). Hydrogen-bonding interactions are depicted in the right panel. c, Conservation and variability in the Rab4 -Rbsn(440 -503) interface. Spheres covered by a semitransparent surface represent Rab4 (left panel) or Rbsn(440 -503) (middle panel). Hydrogen-bonding interactions are depicted in the right panel.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nature (2005, 436, 415-419) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21378754 X.Hou, N.Hagemann, S.Schoebel, W.Blankenfeldt, R.S.Goody, K.S.Erdmann, and A.Itzen (2011).
A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1.
  EMBO J, 30, 1659-1670.
PDB code: 3qbt
20582450 A.Brighouse, J.B.Dacks, and M.C.Field (2010).
Rab protein evolution and the history of the eukaryotic endomembrane system.
  Cell Mol Life Sci, 67, 3449-3465.  
20534488 A.Mishra, S.Eathiraj, S.Corvera, and D.G.Lambright (2010).
Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1).
  Proc Natl Acad Sci U S A, 107, 10866-10871.
PDB code: 3mjh
20059749 A.Sclafani, S.Chen, F.Rivera-Molina, K.Reinisch, P.Novick, and S.Ferro-Novick (2010).
Establishing a role for the GTPase Ypt1p at the late Golgi.
  Traffic, 11, 520-532.  
20048159 D.P.Kloer, R.Rojas, V.Ivan, K.Moriyama, T.van Vlijmen, N.Murthy, R.Ghirlando, P.van der Sluijs, J.H.Hurley, and J.S.Bonifacino (2010).
Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and its interaction with Rab9.
  J Biol Chem, 285, 7794-7804.  
21143914 D.Subramani, and S.K.Alahari (2010).
Integrin-mediated function of Rab GTPases in cancer progression.
  Mol Cancer, 9, 312.  
20070612 E.Kanno, K.Ishibashi, H.Kobayashi, T.Matsui, N.Ohbayashi, and M.Fukuda (2010).
Comprehensive screening for novel rab-binding proteins by GST pull-down assay using 60 different mammalian Rabs.
  Traffic, 11, 491-507.  
20329706 G.D.Henry, D.J.Corrigan, J.V.Dineen, and J.D.Baleja (2010).
Charge effects in the selection of NPF motifs by the EH domain of EHD1.
  Biochemistry, 49, 3381-3392.  
19942850 H.Y.Suh, D.W.Lee, K.H.Lee, B.Ku, S.J.Choi, J.S.Woo, Y.G.Kim, and B.H.Oh (2010).
Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA.
  EMBO J, 29, 496-504.
PDB code: 2wwx
19931244 J.Rahajeng, S.Caplan, and N.Naslavsky (2010).
Common and distinct roles for the binding partners Rabenosyn-5 and Vps45 in the regulation of endocytic trafficking in mammalian cells.
  Exp Cell Res, 316, 859-874.  
20374555 L.S.Mayorga, and E.M.Campoy (2010).
Modeling fusion/fission-dependent intracellular transport of fluid phase markers.
  Traffic, 11, 1001-1015.  
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
19489729 A.Edwards (2009).
Large-scale structural biology of the human proteome.
  Annu Rev Biochem, 78, 541-568.  
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.  
19797056 C.T.Eggers, J.C.Schafer, J.R.Goldenring, and S.S.Taylor (2009).
D-AKAP2 interacts with Rab4 and Rab11 through its RGS domains and regulates transferrin receptor recycling.
  J Biol Chem, 284, 32869-32880.  
19603039 H.Stenmark (2009).
Rab GTPases as coordinators of vesicle traffic.
  Nat Rev Mol Cell Biol, 10, 513-525.  
19119858 J.Wei, Y.Liu, K.Bose, G.D.Henry, and J.D.Baleja (2009).
Disorder and structure in the Rab11 binding domain of Rab11 family interacting protein 2.
  Biochemistry, 48, 549-557.
PDB code: 2k6s
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.  
19442299 P.Mackiewicz, and E.Wyroba (2009).
Phylogeny and evolution of Rab7 and Rab9 proteins.
  BMC Evol Biol, 9, 101.  
19706500 R.M.Nottingham, and S.R.Pfeffer (2009).
Defining the boundaries: Rab GEFs and GAPs.
  Proc Natl Acad Sci U S A, 106, 14185-14186.  
19141279 R.Recacha, A.Boulet, F.Jollivet, S.Monier, A.Houdusse, B.Goud, and A.R.Khan (2009).
Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain.
  Structure, 17, 21-30.
PDB code: 3cwz
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
18949803 T.Uno, T.Moriwaki, M.Nakamura, M.Matsubara, H.Yamagata, K.Kanamaru, and M.Takagi (2009).
Biochemical characterization of rab proteins from Bombyx mori.
  Arch Insect Biochem Physiol, 70, 77-89.  
18685079 H.A.Morrison, H.Dionne, T.E.Rusten, A.Brech, W.W.Fisher, B.D.Pfeiffer, S.E.Celniker, H.Stenmark, and D.Bilder (2008).
Regulation of early endosomal entry by the Drosophila tumor suppressors Rabenosyn and Vps45.
  Mol Biol Cell, 19, 4167-4176.  
  18607085 L.M.Chavas, K.Ihara, M.Kawasaki, R.Kato, T.Izumi, and S.Wakatsuki (2008).
Purification, crystallization and preliminary X-ray crystallographic analysis of Rab27a GTPase in complex with exophilin4/Slp2-a effector.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 599-601.  
18227280 P.M.Mangahas, X.Yu, K.G.Miller, and Z.Zhou (2008).
The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans.
  J Cell Biol, 180, 357-373.  
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
18585354 Y.Cai, H.F.Chin, D.Lazarova, S.Menon, C.Fu, H.Cai, A.Sclafani, D.W.Rodgers, E.M.De La Cruz, S.Ferro-Novick, and K.M.Reinisch (2008).
The structural basis for activation of the Rab Ypt1p by the TRAPP membrane-tethering complexes.
  Cell, 133, 1202-1213.
PDB code: 3cue
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
17503333 D.Jenkins, D.Seelow, F.S.Jehee, C.A.Perlyn, L.G.Alonso, D.F.Bueno, D.Donnai, D.Josifova, D.Josifiova, I.M.Mathijssen, J.E.Morton, K.H.Orstavik, E.Sweeney, S.A.Wall, J.L.Marsh, P.Nurnberg, M.R.Passos-Bueno, and A.O.Wilkie (2007).
RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity.
  Am J Hum Genet, 80, 1162-1170.  
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
17581628 G.Zhu, J.Chen, J.Liu, J.S.Brunzelle, B.Huang, N.Wakeham, S.Terzyan, X.Li, Z.Rao, G.Li, and X.C.Zhang (2007).
Structure of the APPL1 BAR-PH domain and characterization of its interaction with Rab5.
  EMBO J, 26, 3484-3493.
PDB codes: 2q12 2q13
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.  
  16511278 A.Itzen, N.Bleimling, A.Ignatev, O.Pylypenko, and A.Rak (2006).
Purification, crystallization and preliminary X-ray crystallographic analysis of mammalian MSS4-Rab8 GTPase protein complex.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 113-116.  
16882731 B.L.Grosshans, D.Ortiz, and P.Novick (2006).
Rabs and their effectors: achieving specificity in membrane traffic.
  Proc Natl Acad Sci U S A, 103, 11821-11827.  
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
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
16923123 T.Itoh, M.Satoh, E.Kanno, and M.Fukuda (2006).
Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity.
  Genes Cells, 11, 1023-1037.  
17030804 T.Shiba, H.Koga, H.W.Shin, M.Kawasaki, R.Kato, K.Nakayama, and S.Wakatsuki (2006).
Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1.
  Proc Natl Acad Sci U S A, 103, 15416-15421.
PDB code: 2d7c
16905101 W.N.Jagoe, A.J.Lindsay, R.J.Read, A.J.McCoy, M.W.McCaffrey, and A.R.Khan (2006).
Crystal structure of rab11 in complex with rab11 family interacting protein 2.
  Structure, 14, 1273-1283.
PDB codes: 2gzd 2gzh
16855591 X.Pan, S.Eathiraj, M.Munson, and D.G.Lambright (2006).
TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism.
  Nature, 442, 303-306.
PDB code: 2g77
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.