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The "CPC clip motif": a conserved structural signature for heparin-binding proteins.

Torrent M, Nogués MV, Andreu D, Boix E - PLoS ONE (2012)

Bottom Line: However, despite the efforts committed to understand the molecular nature of the interactions in protein-GAG complexes, the answer to this question remains elusive.In the present study the interphases of 20 heparin-binding proteins have been analyzed searching for a conserved structural pattern.The distances between the α carbons and the side chain center of gravity of the residues composing this motif are also conserved.Furthermore, this pattern can be found in other proteins suggested to bind heparin for which no structural information is available.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Biosciences Faculty, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. marc.torrent@uab.cat

ABSTRACT
Glycosaminoglycans (GAGs) are essential molecules that regulate diverse biological processes including cell adhesion, differentiation, signaling and growth, by interaction with a wide variety of proteins. However, despite the efforts committed to understand the molecular nature of the interactions in protein-GAG complexes, the answer to this question remains elusive.In the present study the interphases of 20 heparin-binding proteins have been analyzed searching for a conserved structural pattern. We have found that a structural motif encompassing one polar and two cationic residues (which has been named the CPC clip motif) is conserved among all the proteins deposited in the PDB. The distances between the α carbons and the side chain center of gravity of the residues composing this motif are also conserved. Furthermore, this pattern can be found in other proteins suggested to bind heparin for which no structural information is available. Hence we propose that the CPC clip motif, working like a staple, is a primary contributor to the attachment of heparin and other sulfated GAGs to heparin-binding proteins.

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Molecular docking simulation of Aβ28–123 and Aβ460–569 heparin-binding sites.The figure displays the protein electrostatic potential (left) and the protein cartoon highlighting in red the CPC clip motif (right) of (A) Aβ28–123 and (B) Aβ460–569. CPC residues are colored in blue (cationic) and magenta (polar). Heparin dodecasaccharide ligand used in docking simulations is colored in orange. PDB codes: 1MWR (Aβ28–123), 1TKN (Aβ460–569) and 1HPN (heparin ligand).
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pone-0042692-g005: Molecular docking simulation of Aβ28–123 and Aβ460–569 heparin-binding sites.The figure displays the protein electrostatic potential (left) and the protein cartoon highlighting in red the CPC clip motif (right) of (A) Aβ28–123 and (B) Aβ460–569. CPC residues are colored in blue (cationic) and magenta (polar). Heparin dodecasaccharide ligand used in docking simulations is colored in orange. PDB codes: 1MWR (Aβ28–123), 1TKN (Aβ460–569) and 1HPN (heparin ligand).

Mentions: We have assessed the binding surface of Aβ to heparin by molecular docking simulation on two crystallized fragments of Aβ (Aβ28–123, PDB code 1MWR and Aβ460–569, PDB code 1TKN), both found to bind heparin [39], [40]. As in the case of chemokines and other heparin-binding proteins, both regions are highly cationic (Figure 5).


The "CPC clip motif": a conserved structural signature for heparin-binding proteins.

Torrent M, Nogués MV, Andreu D, Boix E - PLoS ONE (2012)

Molecular docking simulation of Aβ28–123 and Aβ460–569 heparin-binding sites.The figure displays the protein electrostatic potential (left) and the protein cartoon highlighting in red the CPC clip motif (right) of (A) Aβ28–123 and (B) Aβ460–569. CPC residues are colored in blue (cationic) and magenta (polar). Heparin dodecasaccharide ligand used in docking simulations is colored in orange. PDB codes: 1MWR (Aβ28–123), 1TKN (Aβ460–569) and 1HPN (heparin ligand).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412806&req=5

pone-0042692-g005: Molecular docking simulation of Aβ28–123 and Aβ460–569 heparin-binding sites.The figure displays the protein electrostatic potential (left) and the protein cartoon highlighting in red the CPC clip motif (right) of (A) Aβ28–123 and (B) Aβ460–569. CPC residues are colored in blue (cationic) and magenta (polar). Heparin dodecasaccharide ligand used in docking simulations is colored in orange. PDB codes: 1MWR (Aβ28–123), 1TKN (Aβ460–569) and 1HPN (heparin ligand).
Mentions: We have assessed the binding surface of Aβ to heparin by molecular docking simulation on two crystallized fragments of Aβ (Aβ28–123, PDB code 1MWR and Aβ460–569, PDB code 1TKN), both found to bind heparin [39], [40]. As in the case of chemokines and other heparin-binding proteins, both regions are highly cationic (Figure 5).

Bottom Line: However, despite the efforts committed to understand the molecular nature of the interactions in protein-GAG complexes, the answer to this question remains elusive.In the present study the interphases of 20 heparin-binding proteins have been analyzed searching for a conserved structural pattern.The distances between the α carbons and the side chain center of gravity of the residues composing this motif are also conserved.Furthermore, this pattern can be found in other proteins suggested to bind heparin for which no structural information is available.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Biosciences Faculty, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. marc.torrent@uab.cat

ABSTRACT
Glycosaminoglycans (GAGs) are essential molecules that regulate diverse biological processes including cell adhesion, differentiation, signaling and growth, by interaction with a wide variety of proteins. However, despite the efforts committed to understand the molecular nature of the interactions in protein-GAG complexes, the answer to this question remains elusive.In the present study the interphases of 20 heparin-binding proteins have been analyzed searching for a conserved structural pattern. We have found that a structural motif encompassing one polar and two cationic residues (which has been named the CPC clip motif) is conserved among all the proteins deposited in the PDB. The distances between the α carbons and the side chain center of gravity of the residues composing this motif are also conserved. Furthermore, this pattern can be found in other proteins suggested to bind heparin for which no structural information is available. Hence we propose that the CPC clip motif, working like a staple, is a primary contributor to the attachment of heparin and other sulfated GAGs to heparin-binding proteins.

Show MeSH
Related in: MedlinePlus