Structural Insights into Complex Formation of the Axonemal Dynein Light Chain-1 and OADγ Stalk

Abstract

Dyniens are microtubule-based molecular motors that consist of heavy, intermediate, ligh-intermediate and light chains. Intermediate and light chains play a regulatory role in cargo binding or ATPase activity. Most of the dynein accessary chains interact with the N-termini of dynein heavy chains. However, it was recently uncovered that axonemal dynein light chain-1 (LC1) from Chlamydomonas reinhardtii is bound to the microtubule-binding domain (MTBD) of outer arm dynein gamma (OADγ). It was the first discovery that light chain interacts with MTBD. Moreover, it was also discovered that LC1 binding to the MTBD decreases microtubule-binding affinity of the heavy chain. On the other hand, it has been reported that ATPase activity of heavy chain is increased in the presence of microtubules. Thus, both results imply that LC1 indirectly changes ATPase activity of OADγ and tunes ciliary/flagellar beating. However, the molecular mechanism of tuning ATPase activity through the MTBD at the tip of dynein stalk remains unclear. Here, we performed mutational and structural studies of the interaction between LC1 and stalk region and identified two important sites for the interaction. MTBD mainly interacts with LC1 through H5 helix and a flap region which is a characteristic insertion of the axonemal dynein MTBD. Based on these results, we predicted a structural model of LC1-MTBD-Tubulin complex. In this presentation, we will discuss about the structural basis for the LC1-MTBD complex formation that might regulate the function of axonemal dynein heavy chain.