Structural highlights
Function
TIAM1_HUMAN Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA.
Publication Abstract from PubMed
PDZ (PSD-95/Dlg/ZO-1) domains are protein-protein interaction modules often regulated by ligand phosphorylation. Here, we investigated the specificity, structure, and dynamics of Tiam1 PDZ domain/ligand interactions. We show that the PDZ domain specifically binds syndecan1 (SDC1), phosphorylated SDC1 (pSDC1), and SDC3 but not other syndecan isoforms. The crystal structure of the PDZ/SDC1 complex indicates that syndecan affinity is derived from amino acids beyond the four C-terminal residues. Remarkably, the crystal structure of the PDZ/pSDC1 complex reveals a binding pocket that accommodates the phosphoryl group. Methyl relaxation experiments of PDZ/SCD1 and PDZ/pSDC1 complexes reveal that PDZ-phosphoryl interactions dampen dynamic motions in a distal region of the PDZ domain by decoupling them from the ligand-binding site. Our data are consistent with a selection model by which specificity and phosphorylation regulate PDZ/syndecan interactions and signaling events. Importantly, our relaxation data demonstrate that PDZ/phospho-ligand interactions regulate protein dynamics and their coupling to distal sites.
The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics.,Liu X, Shepherd TR, Murray AM, Xu Z, Fuentes EJ Structure. 2013 Mar 5;21(3):342-54. doi: 10.1016/j.str.2013.01.004. Epub 2013 Feb, 7. PMID:23395182[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu X, Shepherd TR, Murray AM, Xu Z, Fuentes EJ. The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics. Structure. 2013 Mar 5;21(3):342-54. doi: 10.1016/j.str.2013.01.004. Epub 2013 Feb, 7. PMID:23395182 doi:http://dx.doi.org/10.1016/j.str.2013.01.004
