Structures and Micelle Locations of the Nonlipidated and Lipidated C-Terminal Membrane Anchor of 2',3'-Cyclic Nucleotide-3'-phosphodiesterase
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- 作者：Cinzia Esposito ; Mario Scrima ; Alfonso Carotenuto ; Annamaria Tedeschi ; Paolo Rovero ; Gerardino D'Errico ; Anna Maria Malfitano ; Maurizio Bifulco ; Anna Maria D'Ursi
- 刊名：Biochemistry
- 出版年：2008
- 出版时间：January 8, 2008
- 年：2008
- 卷：47
- 期：1
- 页码：308 - 319
- 全文大小：1034K
- 年卷期：v.47,no.1(January 8, 2008)
- ISSN：1520-4995
文摘
2,3'-Cyclic nucleotide-3'-phosphodiesterase (CNP) is a myelin-associated protein, an enzymeabundantly present in the central nervous system of mammals and some vertebrates. In vitro, CNPspecifically catalyzes the hydrolysis of 2',3'-cyclic nucleotides to produce 2'-nucleotides, but thephysiologically relevant in vivo substrate is still unknown. Recently, it was found that CNP is a possiblelinker protein between microtubules and the plasma membranes. Since CNP is modified post-translationallyby an isoprenylation process at its C terminus, the prenylation is hypothesized to be a requisite process,which permanently anchors CNP to the plasma membrane. This study investigates the molecular mechanismof the interaction between CNP and the plasma membrane, proposing a general model to interpret thestructural bases of prenylated proteins binding to the membrane. A 13 residue, C-terminal CNP fragment,C13, was demonstrated to be directly responsible for CNP membrane anchoring. C13 and its lipidatedderivative (LIPO-C13) were subjected to conformational analysis in membrane mimetic environments,by means of CD and NMR spectroscopies. The orientation of C13 in relation to the membrane wasinvestigated by NMR and EPR spin labeling studies. Our structural investigation shows that the presenceof the lipidic tail is essential for the peptide to be folded and correctly positioned on the membrane surface.A general model is proposed in which the post-translational lipidation is an important biomolecular trickto enlarge the hydrophobic surface and to enable the contact of the protein with membrane.