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[[Image:Schematic representation of functional domains and phosphorylation sites of PDX-1.jpg|right|580px|thumb|'''Schematic representation of functional domains and phosphorylation sites of PDX-1''']]
[[Image:Schematic representation of functional domains and phosphorylation sites of PDX-1.jpg|right|580px|thumb|'''Schematic representation of functional domains and phosphorylation sites of PDX-1''']]


PDX-1 contains, at the N-terminus, a transactivation domain ( from 1 to 79 amino acids) and the middle region of the protein is composed of a homeodomain (from 146 to 206 amino acids) which is essential for DNA binding and protein-protein interactions.
PDX-1 contains, at the N-terminus, a transactivation domain (from 1 to 79 amino acids) and the middle region of the protein is composed of a homeodomain (from 146 to 206 amino acids) which is essential for DNA binding and protein-protein interactions.




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===='''Motifs of the PDX-1 homeodomain''' [[http://www.proteopedia.org/wiki/index.php/Image:Schematic_representation_of_functional_domains_and_phosphorylation_sites_of_PDX-1.jpg]] ====   
===='''Motifs of the PDX-1 homeodomain''' [http://www.proteopedia.org/wiki/index.php/Image:Schematic_representation_of_functional_domains_and_phosphorylation_sites_of_PDX-1.jpg] ====   


The homeodomain contains a Protein Transduction Domain (PTD : from 188 to 203 amino acids) and a Nuclear Localization Signal motif (NLS : from 197 to 203 amino acids), which allow PDX-1 to permeate into cells.  
The homeodomain contains a Protein Transduction Domain (PTD : from 188 to 203 amino acids) and a Nuclear Localization Signal motif (NLS : from 197 to 203 amino acids), which allow PDX-1 to permeate into cells.  
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Majors differences between conformations A and B  are in the major groove. Three phosphate contacts are specific to conformation A: Asn 51 with Ade 2, and Arg 31 and Lys 46 with Ade 8*. However, conformation B is more specific than conformation A.  
Majors differences between conformations A and B  are in the major groove. Three phosphate contacts are specific to conformation A: Asn 51 with Ade 2, and Arg 31 and Lys 46 with Ade 8*. However, conformation B is more specific than conformation A.  


Actually, in conformation B, Gln 50 formes a water-mediated contact with Gua 5 and Thy 6* , and Asn 51 binds Ade 2 in addition to Ade 3.  
Actually, in conformation B, Gln 50 formes a water-mediated contact with Gua 5 and Thy 6* , and <scene name='56/568027/Asn51/1'>Asn 51</scene> binds Ade 2 in addition to Ade 3.  




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''* The N-terminal arm ''
The <scene name='56/568027/Nterminal/1'>N-terminal arm</scene> (residues 1 to 9) of PDX-1 homeodomain, first contacts the core TAAT bases of the DNA through the minor groove and contributes to the binding specificity. In PDX-1, the N-terminal sequence contains <scene name='56/568027/Basicresidues/2'>three basic residues</scene> :  Lys 2, Arg 3 and Arg 5.
In both PDX-1 conformations, Arg 5 forms hydrogen bonds with the bases of Thy 1 and Gua -1* through the minor groove, and van der Waals contact with Ade 2.
In conformation B, the N-terminal arm is more ordered with Lys 2 hydrogen bonded with the bases Ade 3 and Thy 2* in the minor groove, whereas in the conformation A, the N-terminal arm is mostly disordered. Scientists attributed the different contacts between the two conformations, to differences in DNA bending.
Arg 3 and Arg 43  help the stabilization of the N-terminal arm. In fact, the contact by <scene name='56/568027/Arg/1'>Arg 3 and Arg 43</scene> from the major groove with the phosphate backbone correlates with stabilizing the N-terminal arm. Moreover, these residues are more mobile in conformation A than in conformation B.
So, the most stable  configuration for the N-terminal arm of Pdx1 consists of Lys 2 inserted in the minor groove and Arg 3 outside of the minor grove contacting the phosphate backbone and Arg 43.




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''* The N-terminal arm ''




The N-terminal arm  (residues 1 to 9) of PDX-1 homeodomain, first contacts the core TAAT bases of the DNA through the minor groove and contributes to the binding specificity. In PDX-1, the N-terminal sequence contains three basic residues :  Lys 2, Arg 3 and Arg 5.
In both PDX-1 conformations, Arg 5 forms hydrogen bonds with the bases of Thy 1 and Gua -1* through the minor groove, and van der Waals contact with Ade 2.


In conformation B, the N-terminal arm is more ordered with Lys 2 hydrogen bonded with the bases Ade 3 and Thy 2* in the minor groove, whereas in the conformation A, the N-terminal arm is mostly disordered. Scientists attributed the different contacts between the two conformations, to differences in DNA bending.


Arg 3 and Arg 43  help the stabilization of the N-terminal arm. In fact, the contact by Arg 3 and Arg 43 from the major groove with the phosphate backbone correlates with stabilizing the N-terminal arm. Moreover, these residues are more mobile in conformation A than in conformation B.


So, the most stable  configuration for the N-terminal arm of Pdx1 consists of Lys 2 inserted in the minor groove and Arg 3 outside of the minor grove contacting the phosphate backbone and Arg 43.




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In order to regulate all of these genes, PDX1 interacts with different cofactors.  
In order to regulate all of these genes, PDX1 interacts with different cofactors.  


In pancreatic δ-cells, PDX-1 interacts with PBX1 and PREP1 corresponding respectively to PBC and MEIS proteins. These proteins belong to the three amino acids loop extension (TALE) family of homeodomains. By interacting with these proteins, PDX-1 can regulate the somatostatin promoter. Interaction with the TALE proteins is mediated through a conserved pentapeptide motif, FPWMK, located at the 10 residues of the N-terminal of the homeodomain. <ref>PMID : 11279116</ref>  
In pancreatic δ-cells, PDX-1 interacts with PBX1 and PREP1 corresponding respectively to PBC and MEIS proteins. These proteins belong to the three amino acids loop extension (TALE) family of homeodomains. By interacting with these proteins, PDX-1 can regulate the somatostatin promoter. Interaction with the TALE proteins is mediated through a conserved pentapeptide motif, FPWMK, located in the N-terminal region of the protein and separated from the homeodomain by around 10 residues. <ref>PMID : 11279116</ref>  


In neural cells, PDX-1 utilizes a different binding site on the somatostatin promoter than in δ-cells, suggesting a distinct protein complex. PDX-1 interacts also with the basic helix-loop-helix (bHLH: [http://en.wikipedia.org/wiki/Basic_helix-loop-helix Wikipedia]) factor E47/NeuroD.  
In neural cells, PDX-1 utilizes a different binding site on the somatostatin promoter than in δ-cells, suggesting a distinct protein complex. PDX-1 interacts also with the basic helix-loop-helix (bHLH: [http://en.wikipedia.org/wiki/Basic_helix-loop-helix Wikipedia]) factor E47/NeuroD.  
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