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PDBsum entry 2j6o

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Protein binding PDB id
2j6o
Jmol
Contents
Protein chain
57 a.a. *
Ligands
PRO-LEU-PRO-ARG-
PRO-ARG-VAL
Waters ×46
* Residue conservation analysis
PDB id:
2j6o
Name: Protein binding
Title: Atypical polyproline recognition by the cms n-terminal sh3 domain. Cms:cd2 heterotrimer
Structure: Cd2-associated protein. Chain: a. Fragment: sh3 domain, residues 1-62. Synonym: cas ligand with multiple sh3 domains, adapter protein cms, cms. Engineered: yes. T-cell surface antigen cd2. Chain: c. Fragment: cms binding sequence, residues 324-333.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606
Biol. unit: Dimer (from PDB file)
Resolution:
2.22Å     R-factor:   0.243     R-free:   0.286
Authors: G.Moncalian,N.Cardenes,Y.L.Deribe,M.Spinola-Amilibia, I.Dikic,J.Bravo
Key ref:
G.Moncalián et al. (2006). Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain. J Biol Chem, 281, 38845-38853. PubMed id: 17020880 DOI: 10.1074/jbc.M606411200
Date:
02-Oct-06     Release date:   11-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9Y5K6  (CD2AP_HUMAN) -  CD2-associated protein
Seq:
Struc:
 
Seq:
Struc:
639 a.a.
57 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.M606411200 J Biol Chem 281:38845-38853 (2006)
PubMed id: 17020880  
 
 
Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain.
G.Moncalián, N.Cárdenes, Y.L.Deribe, M.Spínola-Amilibia, I.Dikic, J.Bravo.
 
  ABSTRACT  
 
The CIN85/CMS (human homologs of mouse SH3KBP1/CD2AP) family of endocytic adaptor proteins has the ability to engage multiple effectors and couple cargo trafficking with the cytoskeleton. CIN85 and CMS (Cas ligand with multiple Src homology 3 (SH3) domains) facilitate the formation of large multiprotein complexes required for an efficient internalization of cell surface receptors. It has recently been shown that c-Cbl/Cbl-b could mediate the formation of a ternary complex between one c-Cbl/Cbl-b molecule and two SH3 domains of CIN85, important for the ability of Cbl to promote epidermal growth factor receptor down-regulation. To further investigate whether multimerization is conserved within the family of adaptor proteins, we have solved the crystal structures of the CMS N-terminal SH3 domain-forming complexes with Cbl-b- and CD2-derived peptides. Together with biochemical evidence, the structures support the notion that, despite clear differences in the interaction surface, both Cbl-b and CD2 can mediate multimerization of N-terminal CMS SH3 domains. Detailed analyses on the interacting surfaces also provide the basis for a differential Cbl-b molecular recognition of CMS and CIN85.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. Overall structure of the CMSA·Cbl-b and CMSA·CD2 heterotrimeric complexes and protein/peptide interaction details. A and C, CMSA[SH3I] binds the peptides in a class I orientation (shown in purple), and CMSA[SH3II] recognizes the peptide in class II orientation (shown in gray). The Cbl-b peptide is shown in light blue (A) and CD2 peptide in yellow (B). The A-weighted electron density map around them is contoured at 1.0 . Elements of secondary structure and the positions of the RT, n-Src, and distal loops are indicated. B and D, Schematic representation of contacts between CMSA and the Cbl-b (B) and CD2 (D) peptides (light blue and yellow, respectively). Residues 902, 903, and 904 from the Cbl-b peptide were not visible at the electron density map. Residues 324, 325, and 326 from the CD2 peptide are also disordered. Interactions and residues from SH3I are shown in purple and in gray for SH3II. Dashed lines show hydrogen bonds (labeled with peptide-protein distances in Å), and purple and gray rays designate hydrophobic interactions.
Figure 5.
FIGURE 5. Comparison of the SH3I/Cbl-b interface from CIN85A and CMSA. Electrostatic potential surfaces of SH3 domains from CIN85A/Cbl-b (left) and CMSA/Cbl-b (right) complexes that bind the peptide in a class I-like orientation are shown. The Cbl-b peptides are represented in sticks, and their residues are indicated. n-Src loops are labeled in both structures, and binding pockets are indicated with arrows.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 38845-38853) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20551902 N.Shimokawa, K.Haglund, S.M.Hölter, C.Grabbe, V.Kirkin, N.Koibuchi, C.Schultz, J.Rozman, D.Hoeller, C.H.Qiu, M.B.Londoño, J.Ikezawa, P.Jedlicka, B.Stein, S.W.Schwarzacher, D.P.Wolfer, N.Ehrhardt, R.Heuchel, I.Nezis, A.Brech, M.H.Schmidt, H.Fuchs, V.Gailus-Durner, M.Klingenspor, O.Bogler, W.Wurst, T.Deller, M.H.de Angelis, and I.Dikic (2010).
CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice.
  EMBO J, 29, 2421-2432.  
19633357 P.Fernando, J.S.Sandoz, W.Ding, Y.de Repentigny, S.Brunette, J.F.Kelly, R.Kothary, and L.A.Megeney (2009).
Bin1 SRC homology 3 domain acts as a scaffold for myofiber sarcomere assembly.
  J Biol Chem, 284, 27674-27686.  
19531213 S.Havrylov, Y.Rzhepetskyy, A.Malinowska, L.Drobot, and M.J.Redowicz (2009).
Proteins recruited by SH3 domains of Ruk/CIN85 adaptor identified by LC-MS/MS.
  Proteome Sci, 7, 21.  
17922258 J.L.Ortega Roldan, M.L.Romero Romero, A.Ora, E.Ab, O.Lopez Mayorga, A.I.Azuaga, and N.A.van Nuland (2007).
The high resolution NMR structure of the third SH3 domain of CD2AP.
  J Biomol NMR, 39, 331-336.
PDB code: 2jte
17823309 M.N.Navarro, G.Nusspaumer, P.Fuentes, S.González-García, J.Alcain, and M.L.Toribio (2007).
Identification of CMS as a cytosolic adaptor of the human pTalpha chain involved in pre-TCR function.
  Blood, 110, 4331-4340.  
17428861 Y.Usami, S.Popov, and H.G.Göttlinger (2007).
Potent rescue of human immunodeficiency virus type 1 late domain mutants by ALIX/AIP1 depends on its CHMP4 binding site.
  J Virol, 81, 6614-6622.  
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.