The Micelle-Bound Structure of an Antimicrobial Peptide Derived from the -Chain of Bovine Hemoglobin Isolated from the Tick Booph
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- 作者：Maurí ; cio L. Sforç ; a ; Alessandra Machado ; Rita C. R. Figueredo ; Sé ; rgio Oyama Jr. ; Fernanda D. Silva ; Antonio Miranda ; Sirlei Daffre ; M. Terê ; sa M. Miranda ; Alberto Spisni ; and
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：May 3, 2005
- 年：2005
- 卷：44
- 期：17
- 页码：6440 - 6451
- 全文大小：781K
- 年卷期：v.44,no.17(May 3, 2005)
- ISSN：1520-4995
文摘
Hemoglobin is known to be a source of peptides involved in several functions. The peptideFLSFPTTKTYFPHFDLSHGSAQVKGHGAK (Hb33-61) is a proteolytic product of the bovinehemoglobin 
-chain found in the gut content of the cattle tick, Boophilus microplus, and it possessesantimicrobial activity. Since in the past we showed that the amidated form of Hb33-61, Hb33-61a, isactive against a few Gram-positive bacteria and fungi strains at micromolar concentration [Fogaça et al.(1999) J. Biol. Chem. 274, 25330-25334], we have been prompted to shed more light on its functionaland structural features. Here we show that the peptide is able to disrupt the bacterial membrane ofMicrococcus luteus A270. As for its structure, it has a random conformation in water, and it does notinteract with zwitterionic micelles. On the other hand, it binds to negatively charged micelles acquiringa finite structural organization. The 3D structure of Hb33-61a bound to SDS micelles exhibits anonconventional conformation for an antimicrobial peptide. The backbone is characterized by the presenceof a 
-turn in the N-terminus and by a -turn followed by a -helical stretch in the C-terminus. A hinge,whose spatial organization is stabilized by side-chain-side-chain interactions, joins these two regions.Interestingly, it preserves structural features present in the corresponding segment of the bovine hemoglobin-chain. Hb33-61a does not possess a well-defined amphipathic nature, and H/D exchange experimentsshow that while the C-terminal region is embedded in the SDS micelle, one face of the N-terminal halfis partly exposed to the solvent.
-chain found in the gut content of the cattle tick, Boophilus microplus, and it possessesantimicrobial activity. Since in the past we showed that the amidated form of Hb33-61, Hb33-61a, isactive against a few Gram-positive bacteria and fungi strains at micromolar concentration [Fogaça et al.(1999) J. Biol. Chem. 274, 25330-25334], we have been prompted to shed more light on its functionaland structural features. Here we show that the peptide is able to disrupt the bacterial membrane ofMicrococcus luteus A270. As for its structure, it has a random conformation in water, and it does notinteract with zwitterionic micelles. On the other hand, it binds to negatively charged micelles acquiringa finite structural organization. The 3D structure of Hb33-61a bound to SDS micelles exhibits anonconventional conformation for an antimicrobial peptide. The backbone is characterized by the presenceof a -turn in the N-terminus and by a -turn followed by a -helical stretch in the C-terminus. A hinge,whose spatial organization is stabilized by side-chain-side-chain interactions, joins these two regions.Interestingly, it preserves structural features present in the corresponding segment of the bovine hemoglobin-chain. Hb33-61a does not possess a well-defined amphipathic nature, and H/D exchange experimentsshow that while the C-terminal region is embedded in the SDS micelle, one face of the N-terminal halfis partly exposed to the solvent.