PDBsum entry 6f8f

Ligase

PDB id: 6f8f

Contents

Protein chain

137 a.a.

Ligands

PRO-GLU-GLN-ASP-CYS-ALA-VAL-THR-SER-GLY

Waters ×35

PDB id:

6f8f

Name:

Ligase

Title:

Co-crystal structure of spop math domain and human pdx1 fragment

Structure:

Speckle-type poz protein. Chain: d. Synonym: hib homolog 1,roadkill homolog 1. Engineered: yes. Pancreas/duodenum homeobox protein 1. Chain: g. Synonym: pdx-1,glucose-sensitive factor,gsf,insulin promoter factor 1,ipf-1,insulin upstream factor 1,iuf-1,islet/duodenum homeobox-1, idx-1,somatostatin-transactivating factor 1,stf-1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: spop. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.00Å R-factor: 0.218 R-free: 0.274

Authors:

M.S.Ostertag,G.M.Popowicz,M.Sattler

Key ref:

M.S.Ostertag et al. (2019). The Structure of the SPOP-Pdx1 Interface Reveals Insights into the Phosphorylation-Dependent Binding Regulation. Structure, 27, 327. PubMed id: 30449689 DOI: 10.1016/j.str.2018.10.005

Date:

13-Dec-17 Release date: 28-Nov-18

Protein chain

O43791  (SPOP_HUMAN) -  Speckle-type POZ protein from Homo sapiens

Seq: 374 a.a.

Struc: 137 a.a.

DOI no: 10.1016/j.str.2018.10.005

Structure 27:327 (2019)

PubMed id: 30449689

The Structure of the SPOP-Pdx1 Interface Reveals Insights into the Phosphorylation-Dependent Binding Regulation.

M.S.Ostertag, A.C.Messias, M.Sattler, G.M.Popowicz.

ABSTRACT

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.