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Utilize este identificador para citar ou criar um link para este item: http://acervodigital.unesp.br/handle/11449/17602
Título: 
Role of flanking sequences and phosphorylation in the recognition of the simian-virus-40 large T-antigen nuclear localization sequences by importin-alpha
Autor(es): 
Instituição: 
  • St Vincents Inst Med Res
  • Universidade Estadual Paulista (UNESP)
  • Univ Queensland
  • Szeged Med Univ
  • Australian Natl Univ
  • Monash Univ
ISSN: 
0264-6021
Resumo: 
The nuclear import of simian-virus-40 large T-antigen (tumour antigen) is enhanced via phosphorylation by the protein kinase CK2 at Ser(112) in the vicinity of the NLS (nuclear localization sequence). To determine the structural basis of the effect of the sequences flanking the basic cluster KKKRK, and the effect of phosphorylation on the recognition of the NLS by the nuclear import factor importin-alpha (Impalpha), we co-crystallized non-autoinhibited Impalpha with peptides corresponding to the phosphorylated and non-phosphorylated forms of the NLS, and determined the crystal structures of the complexes. The structures show that the amino acids N-terminally flanking the basic cluster make specific contacts with the receptor that are distinct from the interactions between bipartite NLSs and Impalpha. We confirm the important role of flanking sequences using binding assays. Unexpectedly, the regions of the peptides containing the phosphorylation site do not make specific contacts with the receptor. Binding assays confirm that phosphorylation does not increase the affinity of the T-antigen NLS to Impalpha. We conclude that the sequences flanking the basic clusters in NLSs play a crucial role in nuclear import by modulating the recognition of the NLS by Impalpha, whereas phosphorylation of the T-antigen enhances nuclear import by a mechanism that does not involve a direct interaction of the phosphorylated residue with Impalpha.
Data de publicação: 
15-Out-2003
Citação: 
Biochemical Journal. London: Portland Press, v. 375, p. 339-349, 2003.
Duração: 
339-349
Publicador: 
Portland Press
Palavras-chaves: 
  • importin-alpha (karyopherin-alpha)
  • nuclear localization sequence recognition (NLS recognition)
  • phosphorylation
  • simian-virus-40 (SV40) large tumour-antigen nuclear localization sequence
  • X-ray crystal structure
Fonte: 
http://dx.doi.org/10.1042/BJ20030510
Endereço permanente: 
Direitos de acesso: 
Acesso restrito
Tipo: 
outro
Fonte completa:
http://repositorio.unesp.br/handle/11449/17602
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