Conformational role for the C-terminal tail of theintrinsically disordered high mobility group A (HMGA) chromatin factors
| Autor: | Vincenzo Giancotti, Liam Brady, Laura Arnoldo, Elisa Maurizio, Laetitia Cravello, Barbara Spolaore, Riccardo Sgarra, Guidalberto Manfioletti |
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| Přispěvatelé: | Maurizio, Elisa, Cravello, L, Brady, L, Spolaore, B, Arnoldo, Laura, Giancotti, Vincenzo, Manfioletti, Guidalberto, Sgarra, Riccardo |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Proteomics
Spectrometry Mass Electrospray Ionization Proteolysis Molecular Sequence Data Static Electricity Biology Intrinsically disordered proteins Methylation Biochemistry medicine Humans Amino Acid Sequence Phosphorylation HMGA Proteins medicine.diagnostic_test HMGA General Chemistry Chromatin Recombinant Proteins Protein Structure Tertiary Cell biology Cell Transformation Neoplastic High-mobility group Ion Mobility Chromatin protein - HMGA Mass Spectrometry Conformation Intrinsically disordered proteins Cancer development Protein Processing Post-Translational |
| Popis: | The architectural factors HMGA are highly connected hubs in the chromatin network and affect key cellular functions. HMGA have a causal involvement in cancer development; in fact, truncated or chimeric HMGA forms, resulting from chromosomal rearrangements, lack the constitutively phosphorylated acidic C-terminal tail and display increased oncogenic potential, suggesting a functional role for this domain. HMGA belong to the intrinsically disordered protein category, and this prevents the use of classical approaches to obtain structural data. Therefore, we combined limited proteolysis, ion mobility separation-mass spectrometry (IMS-MS), and electrospray ionization-mass spectrometry (ESI-MS) to obtain structural information regarding full length and C-terminal truncated HMGA forms. Limited proteolysis indicates that HMGA acidic tail shields the inner portions of the protein. IMS-MS and ESI-MS show that HMGA proteins can assume a compact form and that the degree of compactness is dependent upon the presence of the acidic tail and its constitutive phosphorylations. Moreover, we demonstrate that C-terminal truncated forms and wild type proteins are post-translationally modified in a different manner. Therefore, we propose that the acidic tail and its phosphorylation could affect HMGA post-translational modification status and likely their activity. Finally, the mass spectrometry-based approach adopted here proves to be a valuable new tool to obtain structural data regarding intrinsically disordered proteins. |
| Databáze: | OpenAIRE |
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