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PDBsum entry 6f8f
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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 structure of the spop-Pdx1 interface reveals insights into the phosphorylation-Dependent binding regulation.
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Authors
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M.S.Ostertag,
A.C.Messias,
M.Sattler,
G.M.Popowicz.
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Ref.
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Structure, 2019,
27,
327.
[DOI no: ]
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PubMed id
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Abstract
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Pdx1 is a transcription factor crucial for development and maintenance of a
functional pancreas. It regulates insulin expression and glucose homeostasis.
SPOP is an E3-ubiquitin ligase adaptor protein that binds Pdx1, thus triggering
its ubiquitination and proteasomal degradation. However, the underlying
mechanisms are not well understood. Here, we present the crystal structure of
the SPOP-Pdx1 complex. We show that Pdx1 residues 223-233 bind to SPOP MATH
domain with low micromolar affinity. The interface is extended compared to other
SPOP-client proteins. Previously, Pdx1 phosphorylation has been proposed to have
a regulatory function. In this respect we show that phosphorylation lowers the
affinity of Pdx1 to SPOP by isothermal titration calorimetry and nuclear
magnetic resonance data. Our data provide insights into a critical
protein-protein interaction that regulates cellular Pdx1 levels by SPOP-mediated
decay. A reduction of Pdx1 levels in β cells is linked to apoptosis and
considered a hallmark of type 2 diabetes.
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