Abstract
Inflammatory peptides display different types of post-transcriptional modifications, such as C-terminal amidation, that alter their biological activity. Here we describe the structural and molecular dynamics features of the mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF-NH 2), found in the venom of the solitary wasp, and of its carboxyl-free C-terminal form (EMP-AF-COO-) characterized by a reduced activity. Circular dichroism indicates that both peptides switch from a random coil conformation in water to a helical structure in TFE and SDS micelles. NMR data, in 30% TFE, reveal that the two peptides fold into an α-helix spanning most of their length, while they differ in terms of molecular rigidity. To understand the origins of the conformational flexibility observed in the case of EMP-AF-COO-, a 5 ns MD simulation was carried out for each peptide, in an explicit water/TFE environment. The results show that the two peptides differ in an H-bond between Leu14 NH2 and the backbone carbonyl of Ile11. The loss of that H-bond in EMP-AF-COO - leads to a significant modification of its structural dynamics. In fact, as evidenced by essential dynamics analysis, while EMP-AF-NH2 exists mainly as a rigid structure, EMP-AF-COO- presents two helical stretches that fluctuate in some sort of independent fashion. We conclude that the diverse biological activity of the two peptides is not simply due to the reduction of the net positive charge, as generally suggested, but also to a structural perturbation of the amphipathic α-helix that affects their ability to perturb the cell membrane.
| Original language | English |
|---|---|
| Pages (from-to) | 5608-5617 |
| Number of pages | 10 |
| Journal | Biochemistry |
| Volume | 43 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - May 18 2004 |
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ASJC Scopus subject areas
- Biochemistry
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How C-Terminal Carboxyamidation Alters the Biological Activity of Peptides from the Venom of the Eumenine Solitary Wasp. / Sforça, Maurício L.; Oyama, Sérgio; Canduri, Fernanda; Lorenzi, Carla C B; Pertinhez, Thelma A.; Konno, Katsuhiro; Souza, Bibiana M.; Palma, Mário S.; Neto, J. Ruggiero; Azevedo, Walter F.; Spisni, Alberto.
In: Biochemistry, Vol. 43, No. 19, 18.05.2004, p. 5608-5617.Research output: Contribution to journal › Article
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TY - JOUR
T1 - How C-Terminal Carboxyamidation Alters the Biological Activity of Peptides from the Venom of the Eumenine Solitary Wasp
AU - Sforça, Maurício L.
AU - Oyama, Sérgio
AU - Canduri, Fernanda
AU - Lorenzi, Carla C B
AU - Pertinhez, Thelma A.
AU - Konno, Katsuhiro
AU - Souza, Bibiana M.
AU - Palma, Mário S.
AU - Neto, J. Ruggiero
AU - Azevedo, Walter F.
AU - Spisni, Alberto
PY - 2004/5/18
Y1 - 2004/5/18
N2 - Inflammatory peptides display different types of post-transcriptional modifications, such as C-terminal amidation, that alter their biological activity. Here we describe the structural and molecular dynamics features of the mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF-NH 2), found in the venom of the solitary wasp, and of its carboxyl-free C-terminal form (EMP-AF-COO-) characterized by a reduced activity. Circular dichroism indicates that both peptides switch from a random coil conformation in water to a helical structure in TFE and SDS micelles. NMR data, in 30% TFE, reveal that the two peptides fold into an α-helix spanning most of their length, while they differ in terms of molecular rigidity. To understand the origins of the conformational flexibility observed in the case of EMP-AF-COO-, a 5 ns MD simulation was carried out for each peptide, in an explicit water/TFE environment. The results show that the two peptides differ in an H-bond between Leu14 NH2 and the backbone carbonyl of Ile11. The loss of that H-bond in EMP-AF-COO - leads to a significant modification of its structural dynamics. In fact, as evidenced by essential dynamics analysis, while EMP-AF-NH2 exists mainly as a rigid structure, EMP-AF-COO- presents two helical stretches that fluctuate in some sort of independent fashion. We conclude that the diverse biological activity of the two peptides is not simply due to the reduction of the net positive charge, as generally suggested, but also to a structural perturbation of the amphipathic α-helix that affects their ability to perturb the cell membrane.
AB - Inflammatory peptides display different types of post-transcriptional modifications, such as C-terminal amidation, that alter their biological activity. Here we describe the structural and molecular dynamics features of the mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF-NH 2), found in the venom of the solitary wasp, and of its carboxyl-free C-terminal form (EMP-AF-COO-) characterized by a reduced activity. Circular dichroism indicates that both peptides switch from a random coil conformation in water to a helical structure in TFE and SDS micelles. NMR data, in 30% TFE, reveal that the two peptides fold into an α-helix spanning most of their length, while they differ in terms of molecular rigidity. To understand the origins of the conformational flexibility observed in the case of EMP-AF-COO-, a 5 ns MD simulation was carried out for each peptide, in an explicit water/TFE environment. The results show that the two peptides differ in an H-bond between Leu14 NH2 and the backbone carbonyl of Ile11. The loss of that H-bond in EMP-AF-COO - leads to a significant modification of its structural dynamics. In fact, as evidenced by essential dynamics analysis, while EMP-AF-NH2 exists mainly as a rigid structure, EMP-AF-COO- presents two helical stretches that fluctuate in some sort of independent fashion. We conclude that the diverse biological activity of the two peptides is not simply due to the reduction of the net positive charge, as generally suggested, but also to a structural perturbation of the amphipathic α-helix that affects their ability to perturb the cell membrane.
UR - http://www.scopus.com/inward/record.url?scp=18844471721&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18844471721&partnerID=8YFLogxK
U2 - 10.1021/bi0360915
DO - 10.1021/bi0360915
M3 - Article
C2 - 15134435
AN - SCOPUS:18844471721
VL - 43
SP - 5608
EP - 5617
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 19
ER -