| Full text | |
| Author(s): Show less - |
Alves Barbosa, Everton de Almeida
[1]
;
Seraphim, Thiago Vargas
[2]
;
Gandin, Cesar Augusto
[3]
;
Teixeira, Leilane Ferreira
[1]
;
Goncalves da Silva, Ronni Anderson
[1]
;
Righetto, Germanna L.
[4]
;
Goncalves, Kaliandra De Almeida
[4]
;
Vasconcellos, Raphael de Souza
[1]
;
Almeida, Marcia Rogeria
[1]
;
Silva Junior, Abelardo
[5]
;
Rangel Fietto, Juliana Lopes
[1]
;
Kobarg, Jorg
[6, 7]
;
Gileadi, Carina
[8, 9]
;
Massirer, Katlin B.
[9, 10]
;
Borges, Julio Cesar
[2]
;
Neto, Mario de Oliveira
[3]
;
Bressan, Gustavo Costa
[1]
Total Authors: 17
|
| Affiliation: | [1] Univ Fed Vicosa, Dept Bioquim & Biol Mol, Vicosa, MG - Brazil
[2] Univ Sao Paulo, Inst Quim Sao Carlos, Sao Carlos, SP - Brazil
[3] Univ Estadual Paulista, Dept Fis & Biofis, Botucatu, SP - Brazil
[4] Univ Estadual Campinas, Inst Biol, Dept Genet Evolucao Microbiol & Imunol, Campinas, SP - Brazil
[5] Univ Fed Vicosa, Dept Vet, Vicosa, MG - Brazil
[6] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, Campinas, SP - Brazil
[7] Univ Estadual Campinas, Fac Ciencias Farmaceut, Campinas, SP - Brazil
[8] Univ Oxford, Struct Genom Consortium, Old Rd Campus, Res Bldg, Roosevelt Dr, Oxford OX3 7DQ - England
[9] Univ Estadual Campinas, Struct Genom Consortium, Av Dr Andre Tosello 550, Campinas, SP - Brazil
[10] Univ Estadual Campinas, CBMEG, Ctr Mol Biol & Genet Engn, Campinas, SP - Brazil
Total Affiliations: 10
|
| Document type: | Journal article |
| Source: | International Journal of Biological Macromolecules; v. 137, p. 205-214, SEP 15 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
The serine/arginine-rich protein kinase 2 (SRPK2) has been reported as upregulated in several cancer types, with roles in hallmarks such as cell migration, growth, and apoptosis. These findings have indicated that SRPK2 is a promising emerging target in drug discovery initiatives. Although high-resolution models are available for SRPK2 (PDB 2X7G), they have been obtained with a heavily truncated recombinant protein version (-50% of the primary structure), due to the presence of long intrinsically unstructured regions. In the present work, we sought to characterize the structure of a full-length recombinant version of SRPK2 in solution. Low-resolution Small-Angle X-ray Scattering data were obtained for both versions of SRPK2. The truncated Delta N Delta S-SRPK2 presented a propensity to dimerize at higher concentrations whereas the full-length SRPK2 was mainly found as dimers. The hydrodynamic behavior of the full-length SRPK2 was further investigated by analytical size exclusion chromatography and sedimentation velocity analytical ultracentrifugation experiments. SRPK2 behaved as a monomer-dimer equilibrium and both forms have an elongated shape in solution, pointing to a stretched-to closed tendency among the conformational plasticity observed. Taken together, these findings allowed us to define unique structural features of the SRPK2 within SRPK family, characterized by its flexible regions outside the bipartite kinase domain. (C) 2019 Published by Elsevier B.V. (AU) | |
| FAPESP's process: | 14/07206-6 - Studies of the mitochondrial HSP70 of human and protozoa: structural and functional approaches |
| Grantee: | Julio Cesar Borges |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/50724-5 - Protein Kinase Chemical Biology Center: supporting drug development through open-access research |
| Grantee: | Paulo Arruda |
| Support Opportunities: | Research Grants - Research Partnership for Technological Innovation - PITE |
| FAPESP's process: | 11/23110-0 - Using isothermal titration calorimetry for the determination of thermodynamic properties of protein-ligand and protein-protein interactions |
| Grantee: | Julio Cesar Borges |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 12/00195-3 - Post-transcriptional regulatory networks mediated by RNA binding proteins in human pluripotent stem cells |
| Grantee: | Katlin Brauer Massirer |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 17/03489-1 - From functional studies to searching for new inhibitors for cancer: exploring kinases that regulate the cell cycle of the human NEK family |
| Grantee: | Jörg Kobarg |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis |
| Grantee: | Carlos Henrique Inacio Ramos |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/07335-9 - Studies of human HSP70 isoforms residing in the cytoplasm and mitochondria and their high molecular weight oligomers: interaction with co-chaperones and client proteins |
| Grantee: | Julio Cesar Borges |
| Support Opportunities: | Regular Research Grants |