Title (eng)
Structural and functional studies for the disassembly of hemidesmosomes regulated by calcium-calmodulin
Parallel title (eng)
Structural and functional studies for the disassembly of hemidesmosomes regulated by calcium-calmodulin
Author
Jaegeun Song
Advisor
Kristina Djinovic-Carugo
Assessor
Hans Brandstetter
Friedrich Probst
Abstract (eng)
The plectin-integrin β4 complex plays a pivotal role to maintain the mechanical stability of hemidesmosomes in keratinocytes. The binding of calcium-calmodulin (CaM) to plectin isoform 1a contributes to the disruption of the interaction between plectin and integrin β4 together with the phosphorylation on several sites of integrin β4, which results in the disassembly of hemidesmosomes during keratinocyte differentiation and migration. During my PhD thesis, I characterized the interaction between CaM and the actin binding domain of plectin 1a (P1aABD) by ITC and cross-linking assays, and revealed the preferable binding of the N-lobe of CaM (CaMNL) to the N-terminal tail of plectin 1a. I determined the crystal structure of the P1aABD in complex with the N-lobe of CaM to 1.8Å resolution and the entire complex construction was completed by SAXS modeling. The structural analyses show that the disordered N-terminal tail of plectin 1a alters the conformation to α-helix dependent upon the binding of CaM, which is varied into the hydrophobic cleft of (CaMNL).
To shed light on the detailed mechanism of the disassembly of the P1aABD/integrin β4 complex in hemidesmosomes modulated by the binding of calcium-calmodulin to plectin, I also solved the crystal structure of the P1aABD/integrin β4 complex. The dissociation mechanism of the P1aABD/integrin β4 driven by CaM was simulated by displacement ITC experiments and the superposition of two structures. The results suggest that CaM binding causes a steric clash against integrin β4 and promotes the disruption of the plectin-integrin β4 complex. My PhD studies provide the first structural insight into the hemidesmosome disassembly modulated by calcium-calmodulin.
Keywords (eng)
hemidesmosomeintegrin alpha6beta4plectincalmodulinX-ray crystallography
Keywords (deu)
Hemidesmosomeintegrin alpha6beta4plectincalmodulin, X-ray crystallography
Subject (deu)
Subject (deu)
Type (deu)
Persistent identifier
https://phaidra.univie.ac.at/o:1308447
rdau:P60550 (deu)
113 S.
Number of pages
115
Association (deu)
Title (eng)
Structural and functional studies for the disassembly of hemidesmosomes regulated by calcium-calmodulin
Parallel title (eng)
Structural and functional studies for the disassembly of hemidesmosomes regulated by calcium-calmodulin
Author
Jaegeun Song
Abstract (eng)
The plectin-integrin β4 complex plays a pivotal role to maintain the mechanical stability of hemidesmosomes in keratinocytes. The binding of calcium-calmodulin (CaM) to plectin isoform 1a contributes to the disruption of the interaction between plectin and integrin β4 together with the phosphorylation on several sites of integrin β4, which results in the disassembly of hemidesmosomes during keratinocyte differentiation and migration. During my PhD thesis, I characterized the interaction between CaM and the actin binding domain of plectin 1a (P1aABD) by ITC and cross-linking assays, and revealed the preferable binding of the N-lobe of CaM (CaMNL) to the N-terminal tail of plectin 1a. I determined the crystal structure of the P1aABD in complex with the N-lobe of CaM to 1.8Å resolution and the entire complex construction was completed by SAXS modeling. The structural analyses show that the disordered N-terminal tail of plectin 1a alters the conformation to α-helix dependent upon the binding of CaM, which is varied into the hydrophobic cleft of (CaMNL).
To shed light on the detailed mechanism of the disassembly of the P1aABD/integrin β4 complex in hemidesmosomes modulated by the binding of calcium-calmodulin to plectin, I also solved the crystal structure of the P1aABD/integrin β4 complex. The dissociation mechanism of the P1aABD/integrin β4 driven by CaM was simulated by displacement ITC experiments and the superposition of two structures. The results suggest that CaM binding causes a steric clash against integrin β4 and promotes the disruption of the plectin-integrin β4 complex. My PhD studies provide the first structural insight into the hemidesmosome disassembly modulated by calcium-calmodulin.
Keywords (eng)
hemidesmosomeintegrin alpha6beta4plectincalmodulinX-ray crystallography
Keywords (deu)
Hemidesmosomeintegrin alpha6beta4plectincalmodulin, X-ray crystallography
Subject (deu)
Subject (deu)
Type (deu)
Persistent identifier
https://phaidra.univie.ac.at/o:1308448
Number of pages
115
Association (deu)
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