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PDBsum entry 1uti
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Signaling protein regulator
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PDB id
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1uti
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Mona/gads sh3c binding to hematopoietic progenitor kinase 1 (hpk1) combines an atypical sh3 binding motif, R/kxxk, With a classical pxxp motif embedded in a polyproline type ii (ppii) helix.
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Authors
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M.Lewitzky,
M.Harkiolaki,
M.C.Domart,
E.Y.Jones,
S.M.Feller.
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Ref.
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J Biol Chem, 2004,
279,
28724-28732.
[DOI no: ]
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PubMed id
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Abstract
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Hematopoietic progenitor kinase 1 (HPK1) is implicated in signaling downstream
of the T cell receptor. Its non-catalytic, C-terminal half contains several
prolinerich motifs, which have been shown to interact with different SH3
domain-containing adaptor proteins in vitro. One of these, Mona/Gads, was also
shown to bind HPK1 in mouse T cells in vivo. The region of HPK1 that binds to
the Mona/Gads C-terminal SH3 domain has been mapped and shows only very limited
similarity to a recently identified high affinity binding motif in SLP-76,
another T-cell adaptor. Using isothermal titration calorimetry and x-ray
crystallography, the binding of the HPK1 motif to Mona/Gads SH3C has now been
characterized in molecular detail. The results indicate that although charge
interactions through an RXXK motif are essential for complex formation, a PXXP
motif in HPK1 strongly complements binding. This unexpected binding mode
therefore differs considerably from the previously described interaction of
Mona/Gads SH3C with SLP-76. The crystal structure of the complex highlights the
great versatility of SH3 domains, which allows interactions with very different
proteins. This currently limits our ability to categorize SH3 binding properties
by simple rules.
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Figure 2.
FIG. 2. Schematic representation of the Mona/Gads SH3C
domain with the bound HPK1 peptide (P5). The depicted view looks
down the  -barrel arrangement of
the SH3 domain. The PPII helix of P5 is highlighted in green,
and the 3[10] helix is highlighted in orange.
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Figure 5.
FIG. 5. Comparison of the Mona/Gads SH3-HPK1 peptide
complex with other such structures. A, stereo view superposition
of peptides from three different SH3-peptide complexes. SH3
domains are omitted for clarity. The HPK1 is colored (complex
with Mona/Gads SH3C) in green, the Sos peptide (bound to Grb2
SH3N; 1GBQ [PDB]
.pdb) is colored in orange, and the UBPY (USP8) peptide (in
complex with Stam2 SH3; 1UJ0.pdb) is colored in yellow. Peptide
orientation is identical in all three cases with N termini
pointing up. B, detail of the interactions between the RXXK
motif within the HPK1 peptide and Mona/Gads SH3C. C, the
corresponding region from the Sos peptide-Grb2 SH3N complex
(1GBQ [PDB]
.pdb). For clarity, peptide residues are outlined by a light
gray underlay.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
28724-28732)
copyright 2004.
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