PDBsum entry 3rpb

Go to PDB code: 
protein links
Endocytosis/exocytosis PDB id
Protein chain
140 a.a. *
* Residue conservation analysis
PDB id:
Name: Endocytosis/exocytosis
Title: The c2b-domain of rabphilin: structural variations in a janus-faced domain
Structure: Rabphilin 3-a. Chain: a. Fragment: c2b domain. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: de3
NMR struc: 20 models
Authors: J.Ubach,J.Garcia,M.P.Nittler,T.C.Sudhof,J.Rizo
Key ref:
J.Ubach et al. (1999). Structure of the Janus-faced C2B domain of rabphilin. Nat Cell Biol, 1, 106-112. PubMed id: 10559882 DOI: 10.1038/10076
19-Apr-99     Release date:   23-Dec-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P47709  (RP3A_RAT) -  Rabphilin-3A
684 a.a.
140 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     transport   2 terms 
  Biochemical function     transporter activity     1 term  


DOI no: 10.1038/10076 Nat Cell Biol 1:106-112 (1999)
PubMed id: 10559882  
Structure of the Janus-faced C2B domain of rabphilin.
J.Ubach, J.García, M.P.Nittler, T.C.Südhof, J.Rizo.
C2 domains are widespread protein modules that often occur as tandem repeats in many membrane-trafficking proteins such as synaptotagmin and rabphilin. The first and second C2 domains (C2A and C2B, respectively) have a high degree of homology but also specific differences. The structure of the C2A domain of synaptotagmin I has been extensively studied but little is known about the C2B domains. We have used NMR spectroscopy to determine the solution structure of the C2B domain of rabphilin. The overall structure of the C2B domain is very similar to that of other C2 domains, with a rigid beta-sandwich core and loops at the top (where Ca2+ binds) and the bottom. Surprisingly, a relatively long alpha-helix is inserted at the bottom of the domain and is conserved in all C2B domains. Our results, together with the Ca(2+)-independent interactions observed for C2B domains, indicate that these domains have a Janus-faced nature, with a Ca(2+)-binding top surface and a Ca(2+)-independent bottom surface.
  Selected figure(s)  
Figure 3.
Figure 3. Solution structure of the C[2]B domain. a, Backbone superposition of the 20 simulated annealing structures of the C[2]B domain (residues 541 -677). N and C indicate the amino and carboxy termini, respectively. The numbers indicate the positions of several residues to help identify the orientation of the molecule. b, Superposition of the 20 structures showing only the heavy atoms of side chains in a slice of 12 within the centre of the domain. c, Ribbon diagram of the C[2]B domain in the same orientation as a and b. The -strands have been labelled 1 -8 and the positions of the two helices and the Ca^2+-binding region (loops 1 -3) have also been indicated. d, Ribbon diagram of the C[2]B domain in an orientation approximately perpendicular to that of c, which shows how helix 2 runs parallel between the two -sheets. The ribbon diagrams were prepared with the program Molscript49.
Figure 6.
Figure 6. Taxonomy of C[2] domains. a, Topologies of the different subclasses of C[2] domains that have been identified and that we refer to as topologies IA (SytI C[ 2]A domain and PKC- C[2] domain), IB (rabphilin C[ 2]B domain), IIA (PLC- 1 and cPLA[2] C[2] domains) and IIB (PKC- ) (see text). For simplicity, very short -helices within loops of several C[2] domains have not been included in the classification. b, Superpositions of the backbone of the rabphilin C[2]B domain (red) with the backbone of C[2] domains from the other three subclasses (black). The superpositions with SytI C[2]A domain (PDB code 1RSY) and the cPLA[2] C[2] domain (PDB code 1RLW) are shown in the same orientation as Fig. 3a -c . The superposition with the PKC- C[2] domain (PDB code 1BDY) is shown with helix 2 in front, as in Fig. 3d. The positions of secondary structure elements discussed in the text (strand 8 and helix 2) are indicated.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Cell Biol (1999, 1, 106-112) copyright 1999.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21521611 Z.P.Pang, T.Bacaj, X.Yang, P.Zhou, W.Xu, and T.C.Südhof (2011).
Doc2 supports spontaneous synaptic transmission by a Ca(2+)-independent mechanism.
  Neuron, 70, 244-251.  
  20824061 M.Xue, T.K.Craig, O.H.Shin, L.Li, C.A.Brautigam, D.R.Tomchick, T.C.Südhof, C.Rosenmund, and J.Rizo (2010).
Structural and mutational analysis of functional differentiation between synaptotagmins-1 and -7.
  PLoS One, 5, 0.
PDB code: 3n5a
18953334 M.Xue, C.Ma, T.K.Craig, C.Rosenmund, and J.Rizo (2008).
The Janus-faced nature of the C(2)B domain is fundamental for synaptotagmin-1 function.
  Nat Struct Mol Biol, 15, 1160-1168.  
18434502 P.Montaville, N.Coudevylle, A.Radhakrishnan, A.Leonov, M.Zweckstetter, and S.Becker (2008).
The PIP2 binding mode of the C2 domains of rabphilin-3A.
  Protein Sci, 17, 1025-1034.  
18458823 X.Chen, J.Lu, I.Dulubova, and J.Rizo (2008).
NMR analysis of the closed conformation of syntaxin-1.
  J Biomol NMR, 41, 43-54.  
17166855 P.Montaville, C.Schlicker, A.Leonov, M.Zweckstetter, G.M.Sheldrick, and S.Becker (2007).
The C2A-C2B linker defines the high affinity Ca(2+) binding mode of rabphilin-3A.
  J Biol Chem, 282, 5015-5025.
PDB codes: 2cm5 2cm6
17472963 R.V.Stahelin, P.Subramanian, M.Vora, W.Cho, and C.E.Chalfant (2007).
Ceramide-1-phosphate binds group IVA cytosolic phospholipase a2 via a novel site in the C2 domain.
  J Biol Chem, 282, 20467-20474.  
17360437 S.W.Min, W.P.Chang, and T.C.Südhof (2007).
E-Syts, a family of membranous Ca2+-sensor proteins with multiple C2 domains.
  Proc Natl Acad Sci U S A, 104, 3823-3828.  
17719543 S.Wiesner, A.A.Ogunjimi, H.R.Wang, D.Rotin, F.Sicheri, J.L.Wrana, and J.D.Forman-Kay (2007).
Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain.
  Cell, 130, 651-662.
PDB code: 2jqz
17156129 T.Tsuboi, E.Kanno, and M.Fukuda (2007).
The polybasic sequence in the C2B domain of rabphilin is required for the vesicle docking step in PC12 cells.
  J Neurochem, 100, 770-779.  
16515538 A.J.Groffen, R.Friedrich, E.C.Brian, U.Ashery, and M.Verhage (2006).
DOC2A and DOC2B are sensors for neuronal activity with unique calcium-dependent and kinetic properties.
  J Neurochem, 97, 818-833.  
16763567 F.Deák, O.H.Shin, J.Tang, P.Hanson, J.Ubach, R.Jahn, J.Rizo, E.T.Kavalali, and T.C.Südhof (2006).
Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion.
  EMBO J, 25, 2856-2866.  
16790935 M.Biadene, P.Montaville, G.M.Sheldrick, and S.Becker (2006).
Structure of the C2A domain of rabphilin-3A.
  Acta Crystallogr D Biol Crystallogr, 62, 793-799.
PDB code: 2chd
16043482 G.Baldini, A.M.Martelli, G.Tabellini, C.Horn, K.Machaca, P.Narducci, and G.Baldini (2005).
Rabphilin localizes with the cell actin cytoskeleton and stimulates association of granules with F-actin cross-linked by {alpha}-actinin.
  J Biol Chem, 280, 34974-34984.  
15311271 H.Dai, O.H.Shin, M.Machius, D.R.Tomchick, T.C.Südhof, and J.Rizo (2004).
Structural basis for the evolutionary inactivation of Ca2+ binding to synaptotagmin 4.
  Nat Struct Mol Biol, 11, 844-849.
PDB codes: 1w15 1w16
14718922 J.Garcia, S.H.Gerber, S.Sugita, T.C.Südhof, and J.Rizo (2004).
A conformational switch in the Piccolo C2A domain regulated by alternative splicing.
  Nat Struct Mol Biol, 11, 45-53.
PDB code: 1rh8
15217342 T.C.Sudhof (2004).
The synaptic vesicle cycle.
  Annu Rev Neurosci, 27, 509-547.  
12948775 L.K.Tamm, J.Crane, and V.Kiessling (2003).
Membrane fusion: a structural perspective on the interplay of lipids and proteins.
  Curr Opin Struct Biol, 13, 453-466.  
12795692 N.Jarousse, J.D.Wilson, D.Arac, J.Rizo, and R.B.Kelly (2003).
Endocytosis of synaptotagmin 1 is mediated by a novel, tryptophan-containing motif.
  Traffic, 4, 468-478.  
11739399 T.C.Südhof (2002).
Synaptotagmins: why so many?
  J Biol Chem, 277, 7629-7632.  
11340056 A.T.Brunger (2001).
Structure of proteins involved in synaptic vesicle fusion in neurons.
  Annu Rev Biophys Biomol Struct, 30, 157-171.  
11297924 A.T.Brunger (2001).
Structural insights into the molecular mechanism of calcium-dependent vesicle-membrane fusion.
  Curr Opin Struct Biol, 11, 163-173.  
11331402 M.Fukuda, K.Ibata, and K.Mikoshiba (2001).
A unique spacer domain of synaptotagmin IV is essential for Golgi localization.
  J Neurochem, 77, 730-740.  
11285225 S.H.Gerber, J.Garcia, J.Rizo, and T.C.Südhof (2001).
An unusual C(2)-domain in the active-zone protein piccolo: implications for Ca(2+) regulation of neurotransmitter release.
  EMBO J, 20, 1605-1619.  
10851178 A.T.Brunger (2000).
Structural insights into the molecular mechanism of Ca(2+)-dependent exocytosis.
  Curr Opin Neurobiol, 10, 293-302.  
11208133 J.A.Ybe, D.E.Wakeham, F.M.Brodsky, and P.K.Hwang (2000).
Molecular structures of proteins involved in vesicle fusion.
  Traffic, 1, 474-479.  
11114503 K.M.Misura, A.P.May, and W.I.Weis (2000).
Protein-protein interactions in intracellular membrane fusion.
  Curr Opin Struct Biol, 10, 662-671.  
10974000 R.C.Desai, B.Vyas, C.A.Earles, J.T.Littleton, J.A.Kowalchyck, T.F.Martin, and E.R.Chapman (2000).
The C2B domain of synaptotagmin is a Ca(2+)-sensing module essential for exocytosis.
  J Cell Biol, 150, 1125-1136.  
10545502 R.B.Sutton, J.A.Ernst, and A.T.Brunger (1999).
Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca(+2)-independent snare complex interaction.
  J Cell Biol, 147, 589-598.
PDB code: 1dqv
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.