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-Structure paper
Title | The Structure of the Plakin Domain of Plectin Reveals an Extended Rod-like Shape. |
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Journal, issue, pages | J Biol Chem, Vol. 291, Issue 36, Page 18643-18662, Year 2016 |
Publish date | Sep 2, 2016 |
Authors | Esther Ortega / José A Manso / Rubén M Buey / Ana M Carballido / Arturo Carabias / Arnoud Sonnenberg / José M de Pereda / |
PubMed Abstract | Plakins are large multi-domain proteins that interconnect cytoskeletal structures. Plectin is a prototypical plakin that tethers intermediate filaments to membrane-associated complexes. Most plakins ...Plakins are large multi-domain proteins that interconnect cytoskeletal structures. Plectin is a prototypical plakin that tethers intermediate filaments to membrane-associated complexes. Most plakins contain a plakin domain formed by up to nine spectrin repeats (SR1-SR9) and an SH3 domain. The plakin domains of plectin and other plakins harbor binding sites for junctional proteins. We have combined x-ray crystallography with small angle x-ray scattering (SAXS) to elucidate the structure of the plakin domain of plectin, extending our previous analysis of the SR1 to SR5 region. Two crystal structures of the SR5-SR6 region allowed us to characterize its uniquely wide inter-repeat conformational variability. We also report the crystal structures of the SR7-SR8 region, refined to 1.8 Å, and the SR7-SR9 at lower resolution. The SR7-SR9 region, which is conserved in all other plakin domains, forms a rigid segment stabilized by uniquely extensive inter-repeat contacts mediated by unusually long helices in SR8 and SR9. Using SAXS we show that in solution the SR3-SR6 and SR7-SR9 regions are rod-like segments and that SR3-SR9 of plectin has an extended shape with a small central kink. Other plakins, such as bullous pemphigoid antigen 1 and microtubule and actin cross-linking factor 1, are likely to have similar extended plakin domains. In contrast, desmoplakin has a two-segment structure with a central flexible hinge. The continuous versus segmented structures of the plakin domains of plectin and desmoplakin give insight into how different plakins might respond to tension and transmit mechanical signals. |
External links | J Biol Chem / PubMed:27413182 / PubMed Central |
Methods | SAS (X-ray synchrotron) / X-ray diffraction |
Resolution | 1.8 - 3 Å |
Structure data | SASDBA4: SASDBB4: SASDBC4: SASDBD4: SASDBE4: PDB-5j1f: PDB-5j1g: PDB-5j1h: PDB-5j1i: |
Chemicals | ChemComp-1PE: ChemComp-EDO: ChemComp-HOH: |
Source |
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Keywords | STRUCTURAL PROTEIN / CYTOSKELETON / PLAKIN / INTERMEDIATE FILAMENT |