Structural highlights
Disease
DYH1_HUMAN Non-syndromic male infertility due to sperm motility disorder;Primary ciliary dyskinesia. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
DYH1_HUMAN Force generating protein of cilia required for sperm flagellum motility. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required in spermatozoa for the formation of the inner dynein arms and biogenesis of the axoneme (PubMed:24360805).[UniProtKB:Q91XQ0][1]
Publication Abstract from PubMed
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 A 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.
Crystal structure of the stalk region of axonemal inner-arm dynein-d reveals unique features in the coiled-coil and microtubule-binding domain.,Ko S, Toda A, Tanaka H, Yu J, Kurisu G FEBS Lett. 2023 Jul 3. doi: 10.1002/1873-3468.14690. PMID:37400274[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ben Khelifa M, Coutton C, Zouari R, Karaouzène T, Rendu J, Bidart M, Yassine S, Pierre V, Delaroche J, Hennebicq S, Grunwald D, Escalier D, Pernet-Gallay K, Jouk PS, Thierry-Mieg N, Touré A, Arnoult C, Ray PF. Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. Am J Hum Genet. 2014 Jan 2;94(1):95-104. PMID:24360805 doi:10.1016/j.ajhg.2013.11.017
- ↑ Ko S, Toda A, Tanaka H, Yu J, Kurisu G. Crystal structure of the stalk region of axonemal inner-arm dynein-d reveals unique features in the coiled-coil and microtubule-binding domain. FEBS Lett. 2023 Jul 3. PMID:37400274 doi:10.1002/1873-3468.14690
