A Non-Canonical Calmodulin Target Motif Comprising a Polybasic Region and Lipidated Terminal Residue Regulates Localization
Autor: | Masahiro Enomoto, Mitsuhiko Ikura, Christopher B. Marshall, Benjamin M M Grant |
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Rok vydání: | 2020 |
Předmět: |
Models
Molecular Protein Conformation Amino Acid Motifs Protein structure function Review lcsh:Chemistry chemistry.chemical_compound Moiety Protein Isoforms Phosphorylation lcsh:QH301-705.5 Spectroscopy biology myristoylation Lipopeptide General Medicine prenylation Plants Computer Science Applications lipids (amino acids peptides and proteins) Hydrophobic and Hydrophilic Interactions Protein Binding animal structures Calmodulin Static Electricity Protein Prenylation membrane association Catalysis Inorganic Chemistry Proto-Oncogene Proteins p21(ras) Prenylation Humans Calcium Signaling Physical and Theoretical Chemistry Molecular Biology Ca2+ signaling polybasic region Myristoylation protein structure/function KRAS4b Organic Chemistry lcsh:Biology (General) lcsh:QD1-999 chemistry Biophysics biology.protein Calcium Linker |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 2751, p 2751 (2020) |
ISSN: | 1422-0067 |
Popis: | Calmodulin (CaM) is a Ca2+-sensor that regulates a wide variety of target proteins, many of which interact through short basic helical motifs bearing two hydrophobic ‘anchor’ residues. CaM comprises two globular lobes, each containing a pair of EF-hand Ca2+-binding motifs that form a Ca2+-induced hydrophobic pocket that binds an anchor residue. A central flexible linker allows CaM to accommodate diverse targets. Several reported CaM interactors lack these anchors but contain Lys/Arg-rich polybasic sequences adjacent to a lipidated N- or C-terminus. Ca2+-CaM binds the myristoylated N-terminus of CAP23/NAP22 with intimate interactions between the lipid and a surface comprised of the hydrophobic pockets of both lobes, while the basic residues make electrostatic interactions with the negatively charged surface of CaM. Ca2+-CaM binds farnesylcysteine, derived from the farnesylated polybasic C-terminus of KRAS4b, with the lipid inserted into the C-terminal lobe hydrophobic pocket. CaM sequestration of the KRAS4b farnesyl moiety disrupts KRAS4b membrane association and downstream signaling. Phosphorylation of basic regions of N-/C-terminal lipidated CaM targets can reduce affinity for both CaM and the membrane. Since both N-terminal myristoylated and C-terminal prenylated proteins use a Singly Lipidated Polybasic Terminus (SLIPT) for CaM binding, we propose these polybasic lipopeptide elements comprise a non-canonical CaM-binding motif. |
Databáze: | OpenAIRE |
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