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Dynein light chain facilitates dimerization of its primarily monomeric disordered binding partners
Author(s) -
Barbar Elisar,
Hall Justin,
Nyarko Afua
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.673.11
Subject(s) - dynein , dynactin , isothermal titration calorimetry , biophysics , motor protein , chemistry , microbiology and biotechnology , dynein atpase , microtubule , biology , biochemistry
Dynein light chain LC8 was first discovered as an essential component of the microtubule‐based molecular motor dynein. LC8 also interacts with non‐dynein proteins in a broad array of systems, including apoptosis, viral pathogenesis, enzyme regulation, and kidney development. The many diverse interactions of LC8 led to the widely held view that these proteins are dynein cargo, and that LC8 serves as an adaptor for attaching cargo to dynein. Our recent structural and binding studies suggest that LC8 cannot simultaneously assemble with dynein and bind to other proteins. We propose that LC8 functions to facilitate dimerization of its monomeric disordered binding partners. We test this hypothesis by probing the interactions of LC8 with dynein intermediate chain and a non dynein protein Swallow. Both free IC and Swallow are disordered and monomeric at physiological temperature. Using a combination of techniques including fluorescence resonance energy transfer, isothermal titration calorimetry, circular dichroism, NMR and X‐ray crystallography we show that for IC, LC8 binding is coupled to IC self‐association at a dimerization domain distant from the LC8 site, while the rest of IC remains disordered. Likewise, for Swallow, LC8 binding promotes self‐association of the Swa dimerization domain to a stable coiled‐coil.