Development of a novel tetravalent synthetic peptide that binds to phosphatidic acid
| Autor: | Kiyotaka Nishikawa, Kohjiro Nagao, Kentaro Taniuchi, Utako Kato, Takehiko Inaba, Kazunari Akiyoshi, Yoshihiro Sasaki, Toshihide Kobayashi, Miho Watanabe-Takahashi, Yuji Hara, Rina Ogawa, Masato Umeda, Masaki Tsuchiya |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Stereochemistry
Static Electricity lcsh:Medicine Phosphatidic Acids Peptide chemistry.chemical_compound Peptide Library Phosphatidylcholine lcsh:Science Peptide library Phosphatidylethanolamine chemistry.chemical_classification Membranes Multidisciplinary lcsh:R Tryptophan Hydrogen Bonding Phosphatidylserine Phosphatidic acid Amino acid Dissociation constant Kinetics Amino Acid Substitution chemistry Biochemistry lcsh:Q Peptides Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 7, p e0131668 (2015) |
| ISSN: | 1932-6203 |
| Popis: | We employed a multivalent peptide-library screening technique to identify a peptide motif that binds to phosphatidic acid (PA), but not to other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). A tetravalent peptide with the sequence motif of MARWHRHHH, designated as PAB-TP (phosphatidic acid-binding tetravalent peptide), was shown to bind as low as 1 mol% of PA in the bilayer membrane composed of PC and cholesterol. Kinetic analysis of the interaction between PAB-TP and the membranes containing 10 mol% of PA showed that PAB-TP associated with PA with a low dissociation constant of KD = 38 ± 5 nM. Coexistence of cholesterol or PE with PA in the membrane enhanced the PAB-TP binding to PA by increasing the ionization of the phosphomonoester head group as well as by changing the microenvironment of PA molecules in the membrane. Amino acid replacement analysis demonstrated that the tryptophan residue at position 4 of PAB-TP was involved in the interaction with PA. Furthermore, a series of amino acid substitutions at positions 5 to 9 of PAB-TP revealed the involvement of consecutive histidine and arginine residues in recognition of the phosphomonoester head group of PA. Our results demonstrate that the recognition of PA by PABTP is achieved by a combination of hydrophobic, electrostatic and hydrogen-bond interactions, and that the tetravalent structure of PAB-TP contributes to the high affinity binding to PA in the membrane. The novel PA-binding tetravalent peptide PAB-TP will provide insight into the molecular mechanism underlying the recognition of PA by PA-binding proteins that are involved in various cellular events. |
| Databáze: | OpenAIRE |
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