Crystal structure of the stalk region of axonemal inner‐arm dynein‐d reveals unique features in the coiled‐coil and microtubule‐binding domain

Abstract

Axonemal dynein is an ATP‐dependent microtubular motor protein responsible for cilia and flagella beating, and its dysfunction can cause diseases such as primary ciliary dyskinesia and sperm dysmotility. Despite its biological importance, structure‐based mechanisms underlying axonemal dynein motors remain unclear. Here, we determined the X‐ray crystal structure of the human inner‐arm dynein‐d (DNAH1) stalk region, which contains a long antiparallel coiled‐coil and a microtubule‐binding domain (MTBD), at 2.7 Å resolution. Notably, differences in the relative orientation of the coiled‐coil and MTBD in comparison with other dyneins, as well as the diverse orientations of the MTBD flap region among various isoforms, lead us to propose a ‘spike shoe model’ with an altered stepping angle for the interaction between IAD‐d and microtubules. Based on these findings, we discuss isoform‐specific functions of the axonemal dynein stalk MTBDs.