Abstract

Dynein is a large, multisubunit molecular motor that translocates cargoes toward the minus end of microtubules. It contains 2 heavy chains (DHC), several intermediate chains (DIC) and light intermediate chains (DLIC) and a number of light chains (DLC). Specific assembly of the various subunits has to be precise to ensure functioning of Dynein. The intermediate chain (DIC) of cytoplasmic dynein binds to the highly conserved 8-kDa light chain (DLC-8) through a highly conserved 10 aa stretch (reads SYSKETQTPL). A yeast 2-hybrid screen using DLC-8 as bait showed that a wide variety of additional partner candidates exist and that DLC-8 binding proteins contain the consensus sequence (K/R)XTQT. The motif interacts with the common target-accepting grooves of the DLC-8 dimer. The motif binds by beta-augmentation to form a beta-stranded structure in the DLC-8-target peptide complex. The backbone hydrogen bonds are to one DLC-8 monomer while the Q sidechain makes polar interactions with the second molecule. Because it binds to a large number of functionally unrelated proteins, DCL-8 is believed to act as a multifunctional regulatory protein.

A variant motif in nNOS - GIQVD - is found to bind in a similar manner to DLC-8. In yeast, a repeating (VLT)QT motif in the nuclear pore protein nup159 binds to the DLC Dyn2. A KxTQV motif in DIC binds to the DLC TcTex1. It therefore seems likely that other variants of the Q-based DLC interaction motifs will be found.