Comparative modeling of the three CP modules of the beta-chain of C4BP and evaluation of potential sites of interaction with protein S

Bruno Villoutreix, Jose Fernandez, Olle Teleman, John Griffin

Research output: Contribution to journalArticleScientificpeer-review

15 Citations (Scopus)

Abstract

A computer model of the ß-chain of C4b-binding protein (C4BP) was constructed, using the backbone fold of the NMR structures of the sixteenth CP module of factor H (H16) and of a pair of modules consisting of the fifteenth and sixteenth CPs of factor H (H15-16). The characteristic hydrophobic core responsible for dictating the three-dimensional structure of the CP family is conserved in the amino acid sequence of C4BP ßl, ß2 and ß3. The distribution of the electrostatic potential shows that the model is mainly covered by a negative contour. Interestingly, a positive area is observed in the C-terminal region of the first CP module, enclosing peptide 31-45, known to be a binding site for protein S. This observation suggests that electrostatic interactions can be of importance for the interaction of C4BP to protein S. A solvent-accessible hydrophobic patch, located nearby and involving the peptide 31-45, was also found in the model, further confirming that this area is involved in the interaction with protein S. The contribution of ß-chain residues 31-45 to the affinity for protein S was studied further by means of synthetic mutant peptides. The results suggest that both electrostatic and hydrophobic interactions are important for the binding to protein S.
Original languageEnglish
Pages (from-to)1253-1258
JournalProtein Engineering
Volume8
Issue number12
DOIs
Publication statusPublished - 1995
MoE publication typeA1 Journal article-refereed

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Complement C4b-Binding Protein
Protein S
Proteins
Static Electricity
Peptides
Complement Factor H
Electrostatics
Carrier Proteins
Binding sites
Coulomb interactions
Hydrophobic and Hydrophilic Interactions
Computer Simulation
Amino acids
Amino Acid Sequence
Binding Sites
Nuclear magnetic resonance
Amino Acids

Cite this

Villoutreix, Bruno ; Fernandez, Jose ; Teleman, Olle ; Griffin, John. / Comparative modeling of the three CP modules of the beta-chain of C4BP and evaluation of potential sites of interaction with protein S. In: Protein Engineering. 1995 ; Vol. 8, No. 12. pp. 1253-1258.
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abstract = "A computer model of the {\ss}-chain of C4b-binding protein (C4BP) was constructed, using the backbone fold of the NMR structures of the sixteenth CP module of factor H (H16) and of a pair of modules consisting of the fifteenth and sixteenth CPs of factor H (H15-16). The characteristic hydrophobic core responsible for dictating the three-dimensional structure of the CP family is conserved in the amino acid sequence of C4BP {\ss}l, {\ss}2 and {\ss}3. The distribution of the electrostatic potential shows that the model is mainly covered by a negative contour. Interestingly, a positive area is observed in the C-terminal region of the first CP module, enclosing peptide 31-45, known to be a binding site for protein S. This observation suggests that electrostatic interactions can be of importance for the interaction of C4BP to protein S. A solvent-accessible hydrophobic patch, located nearby and involving the peptide 31-45, was also found in the model, further confirming that this area is involved in the interaction with protein S. The contribution of {\ss}-chain residues 31-45 to the affinity for protein S was studied further by means of synthetic mutant peptides. The results suggest that both electrostatic and hydrophobic interactions are important for the binding to protein S.",
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Comparative modeling of the three CP modules of the beta-chain of C4BP and evaluation of potential sites of interaction with protein S. / Villoutreix, Bruno; Fernandez, Jose; Teleman, Olle; Griffin, John.

In: Protein Engineering, Vol. 8, No. 12, 1995, p. 1253-1258.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Comparative modeling of the three CP modules of the beta-chain of C4BP and evaluation of potential sites of interaction with protein S

AU - Villoutreix, Bruno

AU - Fernandez, Jose

AU - Teleman, Olle

AU - Griffin, John

PY - 1995

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N2 - A computer model of the ß-chain of C4b-binding protein (C4BP) was constructed, using the backbone fold of the NMR structures of the sixteenth CP module of factor H (H16) and of a pair of modules consisting of the fifteenth and sixteenth CPs of factor H (H15-16). The characteristic hydrophobic core responsible for dictating the three-dimensional structure of the CP family is conserved in the amino acid sequence of C4BP ßl, ß2 and ß3. The distribution of the electrostatic potential shows that the model is mainly covered by a negative contour. Interestingly, a positive area is observed in the C-terminal region of the first CP module, enclosing peptide 31-45, known to be a binding site for protein S. This observation suggests that electrostatic interactions can be of importance for the interaction of C4BP to protein S. A solvent-accessible hydrophobic patch, located nearby and involving the peptide 31-45, was also found in the model, further confirming that this area is involved in the interaction with protein S. The contribution of ß-chain residues 31-45 to the affinity for protein S was studied further by means of synthetic mutant peptides. The results suggest that both electrostatic and hydrophobic interactions are important for the binding to protein S.

AB - A computer model of the ß-chain of C4b-binding protein (C4BP) was constructed, using the backbone fold of the NMR structures of the sixteenth CP module of factor H (H16) and of a pair of modules consisting of the fifteenth and sixteenth CPs of factor H (H15-16). The characteristic hydrophobic core responsible for dictating the three-dimensional structure of the CP family is conserved in the amino acid sequence of C4BP ßl, ß2 and ß3. The distribution of the electrostatic potential shows that the model is mainly covered by a negative contour. Interestingly, a positive area is observed in the C-terminal region of the first CP module, enclosing peptide 31-45, known to be a binding site for protein S. This observation suggests that electrostatic interactions can be of importance for the interaction of C4BP to protein S. A solvent-accessible hydrophobic patch, located nearby and involving the peptide 31-45, was also found in the model, further confirming that this area is involved in the interaction with protein S. The contribution of ß-chain residues 31-45 to the affinity for protein S was studied further by means of synthetic mutant peptides. The results suggest that both electrostatic and hydrophobic interactions are important for the binding to protein S.

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DO - 10.1093/protein/8.12.1253

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