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N-myristoylated proteins, key components in intracellular signal transduction systems enabling rapid and flexible cell responses.

Hayashi N, Titani K - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions.Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins.On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama-shi, Kanagawa Pref., 226-8501, Japan. nhayashi@bio.titech.ac.jp

ABSTRACT
N-myristoylation, one of the co- or post-translational modifications of proteins, has so far been regarded as necessary for anchoring of proteins to membranes. Recently, we have revealed that N(alpha)-myristoylation of several brain proteins unambiguously regulates certain protein-protein interactions that may affect signaling pathways in brain. Comparison of the amino acid sequences of myristoylated proteins including those in other organs suggests that this regulation is involved in signaling pathways not only in brain but also in other organs. Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions. An algorithm we have developed to identify myristoylated proteins in cells predicts the presence of hundreds of myristoylated proteins. Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins. If the proteins functionally regulated by myristoylation, a posttranslational protein modification, were understood as cross-talk points within the intracellular signal transduction system, known signaling pathways could thus be linked to each other, and a novel map of this intracellular network could be constructed. On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

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Related in: MedlinePlus

pI values and hydrophobicity profiles of the N-terminal amino acid sequences of some members of the predicted myristoylated protein database. pI values were calculated using Protein Identification and Analysis Tools on the ExPASy Server.84) Hydrophobicity profiles were calculated by the Kyte–Doolittle method85) using the Molecular Toolkit of Colorado State University. The attached numbers of each panel correspond to numbers in the list of the predicted myristoylated proteins shown below.
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fig10: pI values and hydrophobicity profiles of the N-terminal amino acid sequences of some members of the predicted myristoylated protein database. pI values were calculated using Protein Identification and Analysis Tools on the ExPASy Server.84) Hydrophobicity profiles were calculated by the Kyte–Doolittle method85) using the Molecular Toolkit of Colorado State University. The attached numbers of each panel correspond to numbers in the list of the predicted myristoylated proteins shown below.

Mentions: A simulation of the membrane binding of a myristoylated domain shows that not only the myristoyl group, but also the N-terminal region, might contribute to the membrane binding.12) Myristoylated proteins have their own myristoyl groups in common. However, their N-terminal amino acid sequences are considerably divergent. The amino acid sequences of the first 10 members in the database of predicted myristoylated proteins exhibit very different pI values and hydrophobicity profiles, as shown in Fig. 10. It can be speculated that a variety of the properties in the N-terminal regions of myristoylated proteins could result from differences in their membrane targeting regions. Both the N-terminal regions of the myristoylated proteins and the contents of their target membranes may exert great influence on the affinities between the proteins and the membranes. In fact, different myristoylated proteins have been isolated from different membrane fractions.54) Furthermore, several groups have reported that different modifications of the amino acid sequences at myristoylated domains altered their localizations in cells.55–57)


N-myristoylated proteins, key components in intracellular signal transduction systems enabling rapid and flexible cell responses.

Hayashi N, Titani K - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

pI values and hydrophobicity profiles of the N-terminal amino acid sequences of some members of the predicted myristoylated protein database. pI values were calculated using Protein Identification and Analysis Tools on the ExPASy Server.84) Hydrophobicity profiles were calculated by the Kyte–Doolittle method85) using the Molecular Toolkit of Colorado State University. The attached numbers of each panel correspond to numbers in the list of the predicted myristoylated proteins shown below.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108300&req=5

fig10: pI values and hydrophobicity profiles of the N-terminal amino acid sequences of some members of the predicted myristoylated protein database. pI values were calculated using Protein Identification and Analysis Tools on the ExPASy Server.84) Hydrophobicity profiles were calculated by the Kyte–Doolittle method85) using the Molecular Toolkit of Colorado State University. The attached numbers of each panel correspond to numbers in the list of the predicted myristoylated proteins shown below.
Mentions: A simulation of the membrane binding of a myristoylated domain shows that not only the myristoyl group, but also the N-terminal region, might contribute to the membrane binding.12) Myristoylated proteins have their own myristoyl groups in common. However, their N-terminal amino acid sequences are considerably divergent. The amino acid sequences of the first 10 members in the database of predicted myristoylated proteins exhibit very different pI values and hydrophobicity profiles, as shown in Fig. 10. It can be speculated that a variety of the properties in the N-terminal regions of myristoylated proteins could result from differences in their membrane targeting regions. Both the N-terminal regions of the myristoylated proteins and the contents of their target membranes may exert great influence on the affinities between the proteins and the membranes. In fact, different myristoylated proteins have been isolated from different membrane fractions.54) Furthermore, several groups have reported that different modifications of the amino acid sequences at myristoylated domains altered their localizations in cells.55–57)

Bottom Line: Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions.Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins.On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama-shi, Kanagawa Pref., 226-8501, Japan. nhayashi@bio.titech.ac.jp

ABSTRACT
N-myristoylation, one of the co- or post-translational modifications of proteins, has so far been regarded as necessary for anchoring of proteins to membranes. Recently, we have revealed that N(alpha)-myristoylation of several brain proteins unambiguously regulates certain protein-protein interactions that may affect signaling pathways in brain. Comparison of the amino acid sequences of myristoylated proteins including those in other organs suggests that this regulation is involved in signaling pathways not only in brain but also in other organs. Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions. An algorithm we have developed to identify myristoylated proteins in cells predicts the presence of hundreds of myristoylated proteins. Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins. If the proteins functionally regulated by myristoylation, a posttranslational protein modification, were understood as cross-talk points within the intracellular signal transduction system, known signaling pathways could thus be linked to each other, and a novel map of this intracellular network could be constructed. On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

Show MeSH
Related in: MedlinePlus