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
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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