4F7R

Crystal structure of 14-3-3 protein from Giardia intestinalis

Summary for 4F7R

• Entry DOI: 10.2210/pdb4f7r/pdb
• Descriptor: 14-3-3 protein, SULFATE ION (2 entities in total)
• Functional Keywords: 9-alpha-helix, homodimer, signal transduction, signaling protein
• Biological source: Giardia intestinalis
• Total number of polymer chains: 4
• Total formula weight: 117631.91

Authors

Fiorillo, A.,Ilari, A.,Lalle, M. (deposition date: 2012-05-16, release date: 2013-05-22, Last modification date: 2024-02-28)

Primary citation

Fiorillo, A.,di Marino, D.,Bertuccini, L.,Via, A.,Pozio, E.,Camerini, S.,Ilari, A.,Lalle, M.
The Crystal Structure of Giardia duodenalis 14-3-3 in the Apo Form: When Protein Post-Translational Modifications Make the Difference.
Plos One, 9:e92902-e92902, 2014

PubMed Abstract: The 14-3-3s are a family of dimeric evolutionary conserved pSer/pThr binding proteins that play a key role in multiple biological processes by interacting with a plethora of client proteins. Giardia duodenalis is a flagellated protozoan that affects millions of people worldwide causing an acute and chronic diarrheal disease. The single giardial 14-3-3 isoform (g14-3-3), unique in the 14-3-3 family, needs the constitutive phosphorylation of Thr214 and the polyglycylation of its C-terminus to be fully functional in vivo. Alteration of the phosphorylation and polyglycylation status affects the parasite differentiation into the cyst stage. To further investigate the role of these post-translational modifications, the crystal structure of the g14-3-3 was solved in the unmodified apo form. Oligomers of g14-3-3 were observed due to domain swapping events at the protein C-terminus. The formation of filaments was supported by TEM. Mutational analysis, in combination with native PAGE and chemical cross-linking, proved that polyglycylation prevents oligomerization. In silico phosphorylation and molecular dynamics simulations supported a structural role for the phosphorylation of Thr214 in promoting target binding. Our findings highlight unique structural features of g14-3-3 opening novel perspectives on the evolutionary history of this protein family and envisaging the possibility to develop anti-giardial drugs targeting g14-3-3.

PubMed: 24658679
DOI: 10.1371/journal.pone.0092902

Experimental method

X-RAY DIFFRACTION (3.2 Å)