Abstract
End-binding proteins (EBs) associate with the growing microtubule plus ends to regulate microtubule dynamics as well as the interaction with intracellular structures. EB3 contributes to pathological vascular leakage through interacting with the inositol 1,4,5-trisphosphate receptor 3 (IP3R3), a calcium channel located at the endoplasmic reticulum membrane. The C-terminal domain of EB3 (residues 200-281) is functionally important for this interaction because it contains the effector binding sites, a prerequisite for EB3 activity and specificity. Structural data for this domain is limited. Here, we report the backbone chemical shift assignments for the human EB3 C-terminal domain and computationally explore its EB3 conformations. Backbone assignments, along with computational models, will allow future investigation of EB3 structural dynamics, interactions with effectors, and will facilitate the development of novel EB3 inhibitors.
Highlights
The microtubule (MT) cytoskeleton undergoes rapid remodeling in response to cellular signals, governing cell shape and polarity [1, 2], cell-cell adhesion [3], cell motility and division [4,5,6], and the spatial organization of intracellular signaling nodes [7, 8]
The End-binding proteins (EBs) family consists of three paralogues, EB1, EB2 and EB3, which share a high degree of sequence homology [21]
The N-terminal region presented by the calponin-homology domain binds the MT tip [22], whereas the C-terminal region is required for dimerization [23,24,25]
Summary
The microtubule (MT) cytoskeleton undergoes rapid remodeling in response to cellular signals, governing cell shape and polarity [1, 2], cell-cell adhesion [3], cell motility and division [4,5,6], and the spatial organization of intracellular signaling nodes [7, 8]. We present NMR assignments and in silico protein structure prediction of the human EB3 C-terminus (residues 200–281). Backbone assignments for the human EB3 C-terminal domain (200–281) were obtained using 350 μM uniformly 13C and 15N-labeled protein and triple resonance NMR experiments [44].
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