N-Terminal Microdomain Peptide from Human Dihydroorotate Dehydrogenase: Structure and Model Membrane Interactions

ISSN: 1875-5305 (Online)
ISSN: 0929-8665 (Print)


Volume 21, 12 Issues, 2014


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Protein & Peptide Letters

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University of Florida
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N-Terminal Microdomain Peptide from Human Dihydroorotate Dehydrogenase: Structure and Model Membrane Interactions

Author(s): Eduardo F. Vicente, Thatyane M. Nobre-Pavinatto, Felippe J. Pavinatto, Osvaldo N. de Oliveira Junior, Antonio J. da Costa Filho and Eduardo M. Cilli

Affiliation: Departamento de Bioquímica e Tecnologia Química, Instituto de Química, UNESP—Univ Estadual Paulista, Rua Prof. Francisco Degni, 55 - CEP 14800-900, Araraquara/SP, Brazil

Abstract

The N-terminus of the human dihydroorotate dehydrogenase (HsDHODH) has been described as important for the enzyme attachment in the inner mitochondrial membrane and possibly to regulate enzymatic activity. In this study, we synthesized the peptide acetyl-GDERFYAEHLMPTLQGLLDPESAHRLAVRFTSLG-amide, comprising the residues 33-66 of HsDHODH N-terminal conserved microdomain. Langmuir monolayers and circular dichroism (CD) were employed to investigate the interactions between the peptide and membrane model, as micelles and monolayers of the lipids phosphatidylcholine (PC), 3-phosphatidylethanolamine (PE) and cardiolipin (CL). These lipids represent the major constituents of inner mitochondrial membranes. According to CD data, the peptide adopted a random structure in water, whereas it acquired α-helical structures in the presence of micelles. The π–A isotherms and polarization-modulated infrared reflection-absorption spectroscopy on monolayers showed that the peptide interacted with all lipids, but in different ways. In DPPC monolayers, the peptide penetrated into the hydrophobic region. The strongest initial interaction occurred with DPPE, but was expelled from this monolayer at high surface pressures. In CL, the peptide could induce a partial dissolution of the monolayer, leading to shorter areas at the monolayer collapse. These results corroborate the literature, where the HsDHODH microdomain is anchored into the inner mitochondrial membrane. Moreover, the existence of distinct conformations and interactions with the different membrane lipids indicates that the access to the enzyme active site may be controlled not only by conformational changes occurring at the microdomain of the protein, but also by some lipid-protein synergetic mechanism, where the HsDHODH peptide would be able to recognize lipid domains in the membrane

Keywords: Circular dichroism, human dihydroorotate dehydrogenase, Langmuir monolayers, peptide, phospholipids, polarization- modulated infrared reflection-absorption spectroscopy, solid-phase peptide synthesis

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Article Details

Volume: 21
First Page: 1
Last Page: 11
Page Count: 11
DOI: 10.2174/0929866521666140508125215
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