PT  - JOURNAL ARTICLE
AU  - Samuel E. Lacey
AU  - Shaoda He
AU  - Sjors H. W. Scheres
AU  - Andrew P. Carter
TI  - Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
AID  - 10.1101/590786
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 590786
4099  - http://biorxiv.org/content/early/2019/03/27/590786.short
4100  - http://biorxiv.org/content/early/2019/03/27/590786.full
AB  - Dyneins are motor proteins responsible for transport in the cytoplasm and the beating of the axoneme in cilia and flagella. They bind and release microtubules via a compact microtubule-binding domain (MTBD) at the end of a long coiled-coil stalk. Here we address how cytoplasmic and axonemal dynein MTBDs bind microtubules at near atomic resolution. We decorated microtubules with MTBDs of cytoplasmic dynein-1 and axonemal dynein DNAH7 and determined their cryo-EM structures using the stand-alone Relion package. We show the majority of the MTBD is remarkably rigid upon binding, with the transition to the high affinity state controlled by the movement of a single helix at the MTBD interface. In addition DNAH7 contains an 18-residue insertion, found in many axonemal dyneins, that reaches over and contacts the adjacent protofilament. Unexpectedly we observe that DNAH7, but not dynein-1, induces large distortions in the microtubule cross-sectional curvature. This raises the possibility that dynein coordination in axonemes is mediated via conformational changes in the microtubule.