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PDBsum entry 1i2m
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protein ligands Protein-protein interface(s) links
Cell cycle PDB id
1i2m

 

 

 

 

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Contents
Protein chains
165 a.a. *
388 a.a. *
Ligands
SO4 ×2
Waters ×475
* Residue conservation analysis
PDB id:
1i2m
Name: Cell cycle
Title: Ran-rcc1-so4 complex
Structure: Gtp-binding nuclear protein ran. Chain: a, c. Synonym: ran. Engineered: yes. Regulator of chromosome condensation 1. Chain: b, d. Fragment: protein truncated from the n-terminal residues 1 to 19. Synonym: rcc1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
1.76Å     R-factor:   0.192     R-free:   0.223
Authors: L.Renault,J.Kuhlmann,A.Henkel,A.Wittinghofer
Key ref:
L.Renault et al. (2001). Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell, 105, 245-255. PubMed id: 11336674 DOI: 10.1016/S0092-8674(01)00315-4
Date:
11-Feb-01     Release date:   02-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P62826  (RAN_HUMAN) -  GTP-binding nuclear protein Ran from Homo sapiens
Seq:
Struc: 		216 a.a.
165 a.a.
Protein chains
Pfam   ArchSchema ?
P18754  (RCC1_HUMAN) -  Regulator of chromosome condensation from Homo sapiens
Seq:
Struc: 		421 a.a.
388 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, C: E.C.3.6.5.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 2: Chains B, D: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
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.

 

 
DOI no: 10.1016/S0092-8674(01)00315-4 Cell 105:245-255 (2001)
PubMed id: 11336674  
 
 
Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1).
L.Renault, J.Kuhlmann, A.Henkel, A.Wittinghofer.
 
  ABSTRACT  
 
RCC1 (regulator of chromosome condensation), a beta propeller chromatin-bound protein, is the guanine nucleotide exchange factor (GEF) for the nuclear GTP binding protein Ran. We report here the 1.8 A crystal structure of a Ran*RCC1 complex in the absence of nucleotide, an intermediate in the multistep GEF reaction. In contrast to previous structures, the phosphate binding region of the nucleotide binding site is perturbed only marginally, possibly due to the presence of a polyvalent anion in the P loop. Biochemical experiments show that a sulfate ion stabilizes the Ran*RCC1 complex and inhibits dissociation by guanine nucleotides. Based on the available structural and biochemical evidence, we present a unified scenario for the GEF mechanism where interaction of the P loop lysine with an acidic residue is a crucial element for the overall reaction.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Overall View of the Ran.RCC1 complex 		Figure 3.
Figure 3. Contact Residues in the Complex
 
  The above figures are reprinted by permission from Cell Press: Cell (2001, 105, 245-255) copyright 2001.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21093592 F.Wu, Y.Liu, Z.Zhu, H.Huang, B.Ding, J.Wu, and Y.Shi (2011).
The 1.9Å crystal structure of Prp20p from Saccharomyces cerevisiae and its binding properties to Gsp1p and histones.
  J Struct Biol, 174, 213-222.
PDB code: 3of7
21176878 S.Tan, and C.A.Davey (2011).
Nucleosome structural studies.
  Curr Opin Struct Biol, 21, 128-136.  
19815619 A.K.Ghosh, C.A.Murga-Zamalloa, L.Chan, P.F.Hitchcock, A.Swaroop, and H.Khanna (2010).
Human retinopathy-associated ciliary protein Retinitis Pigmentosa GTPase Regulator mediates cilia-dependent vertebrate development.
  Hum Mol Genet, 19, 90-98.  
20631154 C.A.Murga-Zamalloa, S.J.Atkins, J.Peranen, A.Swaroop, and H.Khanna (2010).
Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration.
  Hum Mol Genet, 19, 3591-3598.  
20565941 E.Hitakomate, F.E.Hood, H.S.Sanderson, and P.R.Clarke (2010).
The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells.
  BMC Cell Biol, 11, 43.  
20805321 G.Bompard, G.Rabeharivelo, M.Frank, J.Cau, C.Delsert, and N.Morin (2010).
Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis.
  J Cell Biol, 190, 807-822.  
20347844 J.R.England, J.Huang, M.J.Jennings, R.D.Makde, and S.Tan (2010).
RCC1 uses a conformationally diverse loop region to interact with the nucleosome: a model for the RCC1-nucleosome complex.
  J Mol Biol, 398, 518-529.  
20739938 R.D.Makde, J.R.England, H.P.Yennawar, and S.Tan (2010).
Structure of RCC1 chromatin factor bound to the nucleosome core particle.
  Nature, 467, 562-566.
PDB code: 3mvd
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.  
20090203 C.A.Murga-Zamalloa, A.Swaroop, and H.Khanna (2009).
RPGR-containing protein complexes in syndromic and non-syndromic retinal degeneration due to ciliary dysfunction.
  J Genet, 88, 399-407.  
19060893 C.H.Wong, H.Chan, C.Y.Ho, S.K.Lai, K.S.Chan, C.G.Koh, and H.Y.Li (2009).
Apoptotic histone modification inhibits nuclear transport by regulating RCC1.
  Nat Cell Biol, 11, 36-45.  
19335195 C.Thomas, I.Fricke, M.Weyand, and A.Berken (2009).
3D structure of a binary ROP-PRONE complex: the final intermediate for a complete set of molecular snapshots of the RopGEF reaction.
  Biol Chem, 390, 427-435.
PDB code: 2wbl
19696740 D.A.Bonsor, O.Hecht, M.Vankemmelbeke, A.Sharma, A.M.Krachler, N.G.Housden, K.J.Lilly, R.James, G.R.Moore, and C.Kleanthous (2009).
Allosteric beta-propeller signalling in TolB and its manipulation by translocating colicins.
  EMBO J, 28, 2846-2857.
PDB code: 2w8b
19023603 D.C.Soares, P.N.Barlow, D.J.Porteous, and R.S.Devon (2009).
An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin.
  J Mol Model, 15, 113-122.  
19436320 D.Rotin, and S.Kumar (2009).
Physiological functions of the HECT family of ubiquitin ligases.
  Nat Rev Mol Cell Biol, 10, 398-409.  
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.  
19402876 J.J.Wargent, V.C.Gegas, G.I.Jenkins, J.H.Doonan, and N.D.Paul (2009).
UVR8 in Arabidopsis thaliana regulates multiple aspects of cellular differentiation during leaf development in response to ultraviolet B radiation.
  New Phytol, 183, 315-326.  
  20300488 K.Lui, and Y.Huang (2009).
RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking.
  Mol Cell Pharmacol, 1, 148-156.  
18347012 H.Schulze, M.Dose, M.Korpal, I.Meyer, J.E.Italiano, and R.A.Shivdasani (2008).
RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules.
  J Biol Chem, 283, 14109-14119.  
18397376 J.Staal, M.Kaliff, E.Dewaele, M.Persson, and C.Dixelius (2008).
RLM3, a TIR domain encoding gene involved in broad-range immunity of Arabidopsis to necrotrophic fungal pathogens.
  Plant J, 55, 188-200.  
18761691 M.B.Frankel, and L.J.Knoll (2008).
Functional analysis of key nuclear trafficking components reveals an atypical Ran network required for parasite pathogenesis.
  Mol Microbiol, 70, 410-420.  
18617507 M.Sanz-García, I.López-Sánchez, and P.A.Lazo (2008).
Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities.
  Mol Cell Proteomics, 7, 2199-2214.  
18478030 P.R.Clarke, and C.Zhang (2008).
Spatial and temporal coordination of mitosis by Ran GTPase.
  Nat Rev Mol Cell Biol, 9, 464-477.  
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
18762580 Y.Hao, and I.G.Macara (2008).
Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1.
  J Cell Biol, 182, 827-836.  
17506639 A.Cook, F.Bono, M.Jinek, and E.Conti (2007).
Structural biology of nucleocytoplasmic transport.
  Annu Rev Biochem, 76, 647-671.  
17056062 A.Paradise, M.K.Levin, G.Korza, and J.H.Carson (2007).
Significant proportions of nuclear transport proteins with reduced intracellular mobilities resolved by fluorescence correlation spectroscopy.
  J Mol Biol, 365, 50-65.  
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.  
17405150 J.Neidhardt, E.Glaus, D.Barthelmes, C.Zeitz, J.Fleischhauer, and W.Berger (2007).
Identification and characterization of a novel RPGR isoform in human retina.
  Hum Mutat, 28, 797-807.  
17686639 M.C.Lee, and E.A.Miller (2007).
Molecular mechanisms of COPII vesicle formation.
  Semin Cell Dev Biol, 18, 424-434.  
18047743 M.Scheffner, and O.Staub (2007).
HECT E3s and human disease.
  BMC Biochem, 8, S6.  
17287812 M.Stewart (2007).
Molecular mechanism of the nuclear protein import cycle.
  Nat Rev Mol Cell Biol, 8, 195-208.  
17435751 T.Chen, T.L.Muratore, C.E.Schaner-Tooley, J.Shabanowitz, D.F.Hunt, and I.G.Macara (2007).
N-terminal alpha-methylation of RCC1 is necessary for stable chromatin association and normal mitosis.
  Nat Cell Biol, 9, 596-603.  
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
16421734 A.S.Madrid, and K.Weis (2006).
Nuclear transport is becoming crystal clear.
  Chromosoma, 115, 98.  
16371130 E.Hirose, M.Mukai, A.Shimada, H.Nishitani, Y.Shibata, and T.Nishimoto (2006).
Loss of RanGEF/Pim1 activity abolishes the orchestration of Ran-mediated mitotic cellular events in S. pombe.
  Genes Cells, 11, 29-46.  
16717093 L.D.Dahl, H.J.Wieden, M.V.Rodnina, and C.R.Knudsen (2006).
The importance of P-loop and domain movements in EF-Tu for guanine nucleotide exchange.
  J Biol Chem, 281, 21139-21146.  
15906321 A.J.Bordner, and R.Abagyan (2005).
Statistical analysis and prediction of protein-protein interfaces.
  Proteins, 60, 353-366.  
16330762 B.A.Brown, C.Cloix, G.H.Jiang, E.Kaiserli, P.Herzyk, D.J.Kliebenstein, and G.I.Jenkins (2005).
A UV-B-specific signaling component orchestrates plant UV protection.
  Proc Natl Acad Sci U S A, 102, 18225-18230.  
16339730 D.Gogendeau, A.M.Keller, A.Yanagi, J.Cohen, and F.Koll (2005).
Nd6p, a novel protein with RCC1-like domains involved in exocytosis in Paramecium tetraurelia.
  Eukaryot Cell, 4, 2129-2139.  
15688002 K.L.Rossman, C.J.Der, and J.Sondek (2005).
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.
  Nat Rev Mol Cell Biol, 6, 167-180.  
15702987 L.F.Pemberton, and B.M.Paschal (2005).
Mechanisms of receptor-mediated nuclear import and nuclear export.
  Traffic, 6, 187-198.  
15557323 M.G.Jeppesen, T.Navratil, L.L.Spremulli, and J.Nyborg (2005).
Crystal structure of the bovine mitochondrial elongation factor Tu.Ts complex.
  J Biol Chem, 280, 5071-5081.
PDB code: 1xb2
15726638 P.B.Crowley, and A.Golovin (2005).
Cation-pi interactions in protein-protein interfaces.
  Proteins, 59, 231-239.  
15457214 A.M.Lindroth, D.Shultis, Z.Jasencakova, J.Fuchs, L.Johnson, D.Schubert, D.Patnaik, S.Pradhan, J.Goodrich, I.Schubert, T.Jenuwein, S.Khorasanizadeh, and S.E.Jacobsen (2004).
Dual histone H3 methylation marks at lysines 9 and 27 required for interaction with CHROMOMETHYLASE3.
  EMBO J, 23, 4286-4296.  
15457212 E.Futai, S.Hamamoto, L.Orci, and R.Schekman (2004).
GTP/GDP exchange by Sec12p enables COPII vesicle bud formation on synthetic liposomes.
  EMBO J, 23, 4146-4155.  
14973186 J.Korlach, D.W.Baird, A.A.Heikal, K.R.Gee, G.R.Hoffman, and W.W.Webb (2004).
Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled gamma-phosphate-linked GTP analogs.
  Proc Natl Acad Sci U S A, 101, 2800-2805.  
15123651 K.S.Shim, C.Schmutte, G.Tombline, C.D.Heinen, and R.Fishel (2004).
hXRCC2 enhances ADP/ATP processing and strand exchange by hRAD51.
  J Biol Chem, 279, 30385-30394.  
15473836 M.C.Lee, E.A.Miller, J.Goldberg, L.Orci, and R.Schekman (2004).
Bi-directional protein transport between the ER and Golgi.
  Annu Rev Cell Dev Biol, 20, 87.  
15155737 M.Yamada, I.W.Mattaj, and Y.Yoneda (2004).
An ATP-dependent activity that releases RanGDP from NTF2.
  J Biol Chem, 279, 36228-36234.  
15466871 T.J.Hsieh, L.Farh, W.M.Huang, and N.L.Chan (2004).
Structure of the topoisomerase IV C-terminal domain: a broken beta-propeller implies a role as geometry facilitator in catalysis.
  J Biol Chem, 279, 55587-55593.
PDB code: 1wp5
15473863 Y.Zheng (2004).
G protein control of microtubule assembly.
  Annu Rev Cell Dev Biol, 20, 867-894.  
12888511 A.F.Neuwald (2003).
Evolutionary clues to DNA polymerase III beta clamp structural mechanisms.
  Nucleic Acids Res, 31, 4503-4516.  
12671004 A.F.Neuwald, N.Kannan, A.Poleksic, N.Hata, and J.S.Liu (2003).
Ran's C-terminal, basic patch, and nucleotide exchange mechanisms in light of a canonical structure for Rab, Rho, Ras, and Ran GTPases.
  Genome Res, 13, 673-692.  
14984054 C.Harrison (2003).
GrpE, a nucleotide exchange factor for DnaK.
  Cell Stress Chaperones, 8, 218-224.  
14690595 E.Mossessova, R.A.Corpina, and J.Goldberg (2003).
Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism.
  Mol Cell, 12, 1403-1411.
PDB code: 1re0
12604592 H.Y.Li, D.Wirtz, and Y.Zheng (2003).
A mechanism of coupling RCC1 mobility to RanGTP production on the chromatin in vivo.
  J Cell Biol, 160, 635-644.  
12517447 J.Cherfils, and M.Chabre (2003).
Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and Galpha-Ggamma interactions.
  Trends Biochem Sci, 28, 13-17.  
14654833 L.Renault, B.Guibert, and J.Cherfils (2003).
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor.
  Nature, 426, 525-530.
PDB codes: 1r8m 1r8q 1r8r 1r8s 1s9d
12093730 G.Buchwald, A.Friebel, J.E.Galán, W.D.Hardt, A.Wittinghofer, and K.Scheffzek (2002).
Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.
  EMBO J, 21, 3286-3295.
PDB code: 1gzs
11744709 H.J.Wieden, K.Gromadski, D.Rodnin, and M.V.Rodnina (2002).
Mechanism of elongation factor (EF)-Ts-catalyzed nucleotide exchange in EF-Tu. Contribution of contacts at the guanine base.
  J Biol Chem, 277, 6032-6036.  
11889037 K.L.Rossman, D.K.Worthylake, J.T.Snyder, D.P.Siderovski, S.L.Campbell, and J.Sondek (2002).
A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange.
  EMBO J, 21, 1315-1326.
PDB codes: 1kz7 1kzg
12401782 K.L.Rossman, D.K.Worthylake, J.T.Snyder, L.Cheng, I.P.Whitehead, and J.Sondek (2002).
Functional analysis of cdc42 residues required for Guanine nucleotide exchange.
  J Biol Chem, 277, 50893-50898.  
11888276 L.Renault, P.Christova, B.Guibert, S.Pasqualato, and J.Cherfils (2002).
Mechanism of domain closure of Sec7 domains and role in BFA sensitivity.
  Biochemistry, 41, 3605-3612.
PDB code: 1ku1
11932251 M.E.Nemergut, M.E.Lindsay, A.M.Brownawell, and I.G.Macara (2002).
Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor.
  J Biol Chem, 277, 17385-17388.  
12501157 R.L.Rich, and D.G.Myszka (2002).
Survey of the year 2001 commercial optical biosensor literature.
  J Mol Recognit, 15, 352-376.  
11968081 R.Vervoort, and A.F.Wright (2002).
Mutations of RPGR in X-linked retinitis pigmentosa (RP3).
  Hum Mutat, 19, 486-500.  
12194828 W.Moore, C.Zhang, and P.R.Clarke (2002).
Targeting of RCC1 to chromosomes is required for proper mitotic spindle assembly in human cells.
  Curr Biol, 12, 1442-1447.  
11948780 Y.Qi, J.Pei, and N.V.Grishin (2002).
C-terminal domain of gyrase A is predicted to have a beta-propeller structure.
  Proteins, 47, 258-264.  
11685227 A.E.Karnoub, D.K.Worthylake, K.L.Rossman, W.M.Pruitt, S.L.Campbell, J.Sondek, and C.J.Der (2001).
Molecular basis for Rac1 recognition by guanine nucleotide exchange factors.
  Nat Struct Biol, 8, 1037-1041.  
11573088 D.Lim, H.U.Park, L.De Castro, S.G.Kang, H.S.Lee, S.Jensen, K.J.Lee, and N.C.Strynadka (2001).
Crystal structure and kinetic analysis of beta-lactamase inhibitor protein-II in complex with TEM-1 beta-lactamase.
  Nat Struct Biol, 8, 848-852.
PDB codes: 1jtd 1jtg
11729264 I.G.Macara (2001).
Transport into and out of the nucleus.
  Microbiol Mol Biol Rev, 65, 570.  
11701921 I.R.Vetter, and A.Wittinghofer (2001).
The guanine nucleotide-binding switch in three dimensions.
  Science, 294, 1299-1304.  
11738594 K.D.Corbett, and T.Alber (2001).
The many faces of Ras: recognition of small GTP-binding proteins.
  Trends Biochem Sci, 26, 710-716.  
11733047 S.M.Steggerda, and B.M.Paschal (2001).
Identification of a conserved loop in Mog1 that releases GTP from Ran.
  Traffic, 2, 804-811.  
11566135 S.Padmanabhan, and D.M.Freymann (2001).
The conformation of bound GMPPNP suggests a mechanism for gating the active site of the SRP GTPase.
  Structure, 9, 859-867.
PDB codes: 1jpj 1jpn
11595749 Y.Gao, J.Xing, M.Streuli, T.L.Leto, and Y.Zheng (2001).
Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors.
  J Biol Chem, 276, 47530-47541.  
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.

 

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