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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Human FEZ1 has characteristics of a natively unfolded protein and dimerizes in solution

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Author(s):
Lanza, Daniel C. F. [1] ; Silva, Julio C. [2] ; Assmann, Eliana M. ; Quaresma, Alexandre J. C. [1] ; Bressan, Gustavo C. [1] ; Torriani, Iris L. [2] ; Kobarg, Joerg [1, 3]
Total Authors: 7
Affiliation:
[1] Univ Estadual Campinas, Inst Biol, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Inst Fis Gleb Wataghin, Campinas, SP - Brazil
[3] Lab Nacl Luz Sincrotron, Ctr Biol Mol Estrutural, BR-13084971 Campinas, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS; v. 74, n. 1, p. 104-121, JAN 2009.
Web of Science Citations: 23
Abstract

The fasciculation and elongation protein Zeta 1 (FEZ1) is the mammalian orthologue of the Caenorhabditis elegans protein UNC-76, which is necessary for axon growth. Human FEZ1 interacts with Protein Kinase C (PKC) and several regulatory proteins involved in functions ranging from microtubule associated transport to transcriptional regulation. Theoretical prediction, circular dichroism, fluorescence spectroscopy, and limited proteolysis of recombinant FEZ1 suggest that it contains disordered regions, especially in its N-terminal region, and that it may belong to the group of natively unfolded proteins. Small angle X-ray scattering experiments indicated a mainly disordered conformation, proved that FEZ1 is a dimer of elongated shape and provided overall dimensional parameters for the protein. In vitro pull down experiments confirmed these results and demonstrated that dimerization involves the N-terminus. Ab-initio 3D low resolution models of the full-length conformation of the dimeric constructs 6xHis-FEZ1(1-392) and 6xHis-FEZ1(1-227) were obtained. Furthermore, we performed in vitro phosphorylation assays of FEZ1 with PKC. The phosphorylation occur-red mainly in its C-terminal region, and does not cause any significant conformational changes, but nonetheless inhibited its interaction with the FEZ1 interacting domain of the protein CLASP2 in vitro. The C terminus of FEZ1 has been reported to bind to several interacting proteins. This suggests that FEZ1 binding and transport function of interacting proteins may be subject to regulation by phosphorylation. (AU)

FAPESP's process: 05/00235-1 - Functional and structural studies of three human regulatory proteins: Fez1, Ki-1/57 and NSAP1 (hnRNP-Q)
Grantee:Jörg Kobarg
Support Opportunities: Regular Research Grants