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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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Related in: MedlinePlus

Summary of side-chain amino acid interactions for protein-heparin complexes deposited in the PDB.Molecular contacts were inspected for (A) SGN and (B) IDS, the two major components of heparin. The fraction of contacts is represented for each amino acid.
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pone-0042692-g001: Summary of side-chain amino acid interactions for protein-heparin complexes deposited in the PDB.Molecular contacts were inspected for (A) SGN and (B) IDS, the two major components of heparin. The fraction of contacts is represented for each amino acid.

Mentions: At present, 20 non-redundant three-dimensional protein structures in complex with heparin disaccharides or oligosaccharides have been deposited in the PDB. Using the PDBeMOTIF server we have examined them to identify the protein primary amino acid residues that interact with the two main components of heparin, N,O6-disulfo-glucosamine (SGN) and 2-O-sulfo-α-L-iduronic acid (IDS). We have inspected the amino acid side chains for hydrogen bonding, electrostatic and van der Waals interactions with heparin. The results (Figure 1) confirm that Arg and Lys are essential, making most of the electrostatic and hydrogen-bonding interactions with both IDS and SGN.


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

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

Summary of side-chain amino acid interactions for protein-heparin complexes deposited in the PDB.Molecular contacts were inspected for (A) SGN and (B) IDS, the two major components of heparin. The fraction of contacts is represented for each amino acid.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0042692-g001: Summary of side-chain amino acid interactions for protein-heparin complexes deposited in the PDB.Molecular contacts were inspected for (A) SGN and (B) IDS, the two major components of heparin. The fraction of contacts is represented for each amino acid.
Mentions: At present, 20 non-redundant three-dimensional protein structures in complex with heparin disaccharides or oligosaccharides have been deposited in the PDB. Using the PDBeMOTIF server we have examined them to identify the protein primary amino acid residues that interact with the two main components of heparin, N,O6-disulfo-glucosamine (SGN) and 2-O-sulfo-α-L-iduronic acid (IDS). We have inspected the amino acid side chains for hydrogen bonding, electrostatic and van der Waals interactions with heparin. The results (Figure 1) confirm that Arg and Lys are essential, making most of the electrostatic and hydrogen-bonding interactions with both IDS and SGN.

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