The human alpha(2)-plasmin inhibitor: functional characterization of the unique plasmin(ogen)-binding region
| Autor: | Sofia Lejon, Simon S. Gerber, Michael Locher, Johann Schaller |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Plasmin Protein Conformation Mutant Lysine Molecular Sequence Data Biology medicine.disease_cause Kringle domain law.invention Cellular and Molecular Neuroscience Sulfation Kringles law medicine Animals Humans Amino Acid Sequence Fibrinolysin Molecular Biology Escherichia coli Pharmacology alpha-2-Antiplasmin Binding Sites Binding process Plasminogen Cell Biology Recombinant Proteins Biochemistry Recombinant DNA Molecular Medicine Peptides Sequence Alignment medicine.drug Protein Binding |
| Zdroj: | Gerber, Simon S.; Lejon, Sofia; Locher, Michael; Schaller, Johann (2010). The human alpha(2)-plasmin inhibitor: functional characterization of the unique plasmin(ogen)-binding region. Cellular and molecular life sciences, 67(9), pp. 1505-1518. Basel: SP Birkhäuser Verlag Basel 10.1007/s00018-010-0264-3 |
| DOI: | 10.1007/s00018-010-0264-3 |
| Popis: | The human alpha(2)-plasmin inhibitor (A2PI) possesses unique N- and C-terminal extensions that significantly influence its biological activities. The C-terminal segment, A2PIC (Asn(398)-Lys(452)), contains six lysines thought to be involved in the binding to lysine-binding sites in the kringle domains of human plasminogen, of which four (Lys(422), Lys(429), Lys(436), Lys(452)) are completely and two (Lys(406), Lys(415)) are partially conserved. Multiple Lys to Ala mutants of A2PIC were expressed in Escherichia coli and used in intrinsic fluorescence titrations with kringle domains K1, K4, K4 + 5, and K1 + 2 + 3 of human plasminogen. We were able to identify the C-terminal Lys(452) as the main binding partner in recombinant A2PIC (rA2PIC) constructs with isolated kringles. We could show a cooperative, zipper-like enhancement of the interaction between C-terminal Lys(452) and internal Lys(436) of rA2PIC and isolated K1 + 2 + 3, whereas the other internal lysine residues contribute only to a minor extent to the binding process. Sulfated Tyr(445) in the unique C-terminal segment revealed no influence on the binding affinity to kringle domains. |
| Databáze: | OpenAIRE |
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