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PDBsum entry 4gzu
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Signaling protein
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PDB id
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4gzu
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References listed in PDB file
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Key reference
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Title
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Structural basis for autoinhibition of the guanine nucleotide exchange factor farp2.
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Authors
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X.He,
Y.C.Kuo,
T.J.Rosche,
X.Zhang.
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Ref.
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Structure, 2013,
21,
355-364.
[DOI no: ]
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PubMed id
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Abstract
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FARP2 is a Dbl-family guanine nucleotide exchange factor (GEF) that contains a
4.1, ezrin, radixin and moesin (FERM) domain, a Dbl-homology (DH) domain and two
pleckstrin homology (PH) domains. FARP2 activates Rac1 or Cdc42 in response to
upstream signals, thereby regulating processes such as neuronal axon guidance
and bone homeostasis. How the GEF activity of FARP2 is regulated remained poorly
understood. We have determined the crystal structures of the catalytic DH domain
and the DH-PH-PH domains of FARP2. The structures reveal an auto-inhibited
conformation in which the GEF substrate-binding site is blocked collectively by
the last helix in the DH domain and the two PH domains. This conformation is
stabilized by multiple interactions among the domains and two well-structured
inter-domain linkers. Our cell-based activity assays confirm the suppression of
the FARP2 GEF activity by these auto-inhibitory elements.
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