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PDBsum entry 2bzy
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References listed in PDB file
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Key reference
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Title
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The c-Terminal sh3 domain of crkl as a dynamic dimerization module transiently exposing a nuclear export signal.
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Authors
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M.Harkiolaki,
R.J.Gilbert,
E.Y.Jones,
S.M.Feller.
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Ref.
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Structure, 2006,
14,
1741-1753.
[DOI no: ]
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PubMed id
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Abstract
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CRKL plays essential roles in cell signaling. It consists of an N-terminal SH2
domain followed by two SH3 domains. SH2 and SH3N bind to signaling proteins, but
the function of the SH3C domain has remained largely enigmatic. We show here
that the SH3C of CRKL forms homodimers in protein crystals and in solution.
Evidence for dimer formation of full-length CRKL is also presented. In the SH3C
dimer, a nuclear export signal (NES) is mostly buried under the domain surface.
The same is true for a monomeric SH3C obtained under different crystallization
conditions. Interestingly, partial SH3 unfolding, such as occurs upon
dimer/monomer transition, produces a fully-accessible NES through translocation
of a single beta strand. Our results document the existence of an SH3 domain
dimer formed through exchange of the first SH3 domain beta strand and suggest
that partial unfolding of the SH3C is important for the relay of information in
vivo.
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Figure 2.
Figure 2. The CRKL SH3C Dimer
Schematic representation
of the CRKL SH3C dimer (A), where the two polypeptide chains are
colored green and red, respectively, with all β strands
numbered from N to C terminus and a second view of the same
structure (B) produced through a 90° clockwise rotation
around the x axis of (A). The second orientation (B) is also
viewed as a space-filling model (C). (D) C[α] models of the
SH3C dimer and superimposed monomers. The two polypeptide chains
in the dimer are colored green and red, respectively, while the
monomers are in gray. The structures were superimposed in LSQKAB
(Kabsch, 1976) with equivalences of core SH3 fold residues
across species. Orientation same as in (A).
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Figure 6.
Figure 6. Examples of Known SH3 Dimers
Ribbon
representations of SH3 fold dimers (partner subunit polypeptide
chains in green and red, respectively) of Vav and Grb2 (A)
(Nishida et al., 2001), Grap2 (Mona/Gads) (B) (Harkiolaki et
al., 2003), KorB-C (C), p47^phox (D) (Delbruck et al., 2002),
and Eps8 (E) (Kishan et al., 1997). The yellow circle in (B)
represents a crucial divalent metal ion.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2006,
14,
1741-1753)
copyright 2006.
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