A class III PDZ binding motif in the myotilin and FATZ families binds enigma family proteins: a common link for Z-disc myopathies
| Autor: | Giorgio Valle, Georgine Faulkner, Heli Suila, Mohamed Ismail, Pernilla von Nandelstadh, Anna Belgrano, Ivano Zara, Chiara Gardin, Olli Carpén |
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| Rok vydání: | 2008 |
| Předmět: |
PDZ domain
Amino Acid Motifs Molecular Sequence Data Muscle Proteins Actinin Biology Muscle disorder Ligands Sarcomere Binding Competitive 03 medical and health sciences Mice 0302 clinical medicine Muscular Diseases Myosin Chlorocebus aethiops Myotilin Animals Humans Connectin Amino Acid Sequence Phosphorylation Molecular Biology Actin Conserved Sequence 030304 developmental biology Adaptor Proteins Signal Transducing 0303 health sciences C-terminus Microfilament Proteins Cell Biology Articles LIM Domain Proteins Cyclic AMP-Dependent Protein Kinases Cell biology Protein Structure Tertiary Rats Cytoskeletal Proteins Biochemistry Organ Specificity COS Cells Calcium-Calmodulin-Dependent Protein Kinase Type 2 Carrier Proteins Peptides 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Molecular and cellular biology. 29(3) |
| ISSN: | 1098-5549 |
| Popis: | Interactions between Z-disc proteins regulate muscle functions and disruption of these interactions results in muscle disorders. Mutations in Z-disc components myotilin, ZASP/Cypher, and FATZ-2 (calsarcin-1/ myozenin-2) are associated with myopathies. We report here that the myotilin and the FATZ (calsarcin/ myozenin) families share high homology at their final C-terminal five amino acids. This C-terminal E[ST] [DE][DE]L motif is present almost exclusively in these families and is evolutionary conserved. We show by in vitro and in vivo studies that proteins from the myotilin and FATZ (calsarcin/myozenin) families interact via this novel type of class III PDZ binding motif with the PDZ domains of ZASP/Cypher and other Enigma family members: ALP, CLP-36, and RIL. We show that the interactions can be modulated by phosphorylation. Calmodulin-dependent kinase II phosphorylates the C terminus of FATZ-3 (calsarcin-3/myozenin-3) and myotilin, whereas PKA phosphorylates that of FATZ-1 (calsarcin-2/myozenin-1) and FATZ-2 (calsarcin-1/ myozenin-1). This is the first report of a binding motif common to both the myotilin and the FATZ (calsarcin/ myozenin) families that is specific for interactions with Enigma family members. The sarcomere of striated muscle consists of strictly organized subunits, myosin-containing thick filaments and actincontaining thin filaments. The thin filaments are aligned and cross-linked at the Z-discs by a molecular complex in which -actinin is one of the core structures. Since the contractile force is transduced via the Z-discs, this structure has special requirements. It must provide extensive stability and yet undergo modulation in response to external signals. The Z-discs also serve as important sensors of extracellular cues and me |
| Databáze: | OpenAIRE |
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