FC0081
Dynein intermediate chain (IC)  -  Dynein regulator protein (NudE)

Biological function
Cytoplasmic dynein, a microtubule-associated minus-end directed molecular motor, is responsible for many aspects of intracellular transport, including chromosome segregation, mitotic spindle positioning and assembly, and regulation of the spindle assembly checkpoint. Emerging evidence suggests that the functional diversity of the dynein complex is in part due to an array of accessory regulatory proteins that are not stoichiometric components of the dynein complex.

Structural evidence
Specific residues within IC that interact with NudE are a subset of the bi-segmental binding region, preferably region 1 of the bi- segmental binding. NudE-bound IC has increased flexibility on the faster time scale in region 2, evidenced by lower heteronuclear NOE values relative to apo-IC. In the nNudE-bound protein, residues 41– 47 and 62– 87 become slightly more ordered, whereas residues 48 – 61 become slightly more disordered. These data suggest that the nascent helix observed in this region in the unbound IC is not stabilized upon binding but on the contrary becomes slightly more disordered.

Biochemical evidence
K_D for IC 1-40 (primary binding region) is 1.7 μM, IC 1-87 is 2.5 μM, IC1-143 2.2 μM, suggesting a slight competition with intermolecular interactions when region 2 is present. Modifications in region 2 regulate p150^Glued binding.

Mechanism category
competitive binding, flexibility modulation

Posttranslational modification
Residue-specific structural changes in and near region 2 likely may diminish or enhance dynactin binding with limited effect on NudE binding. Phosphorylation indeed results in reduced binding to p150^Glued

Isoforms, context-dependence
Region 2 and in linker 2 are rich in potential phosphorylation and alternative splicing sites. AS modification of region 2 could interfere with p150^Glued binding but have a limited effect on NudE binding.

Significance
Fuzziness enables a bi-segmental binding region of IC as well as in region 2 and flanking linkers it plays a role in selecting which regulatory protein binds IC.

Submitted by
Elisar Barbar   barbare@science.oregonstate.edu