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PDBsum entry 2j6f
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Protein binding
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PDB id
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2j6f
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References listed in PDB file
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Key reference
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Title
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Atypical polyproline recognition by the cms n-Terminal src homology 3 domain.
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Authors
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G.Moncalián,
N.Cárdenes,
Y.L.Deribe,
M.Spínola-Amilibia,
I.Dikic,
J.Bravo.
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Ref.
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J Biol Chem, 2006,
281,
38845-38853.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
38845-38853)
copyright 2006.
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