8RGI

Structure of DYNLT1:DYNLT2B (TCTEX1:TCTEX1D2) heterodimer.

Summary for 8RGI

• Entry DOI: 10.2210/pdb8rgi/pdb
• Descriptor: Dynein light chain Tctex-type 1, Dynein light chain Tctex-type protein 2B (2 entities in total)
• Functional Keywords: dynein, cilia, intraflagellar transport, complex, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 28513.02

Authors

Mukhopadhyay, A.G.,Toropova, K.,Daly, L.,Wells, J.,Vuolo, L.,Seda, M.,Jenkins, D.,Stephens, D.J.,Roberts, A.J. (deposition date: 2023-12-13, release date: 2024-03-20, Last modification date: 2024-04-10)

Primary citation

Mukhopadhyay, A.G.,Toropova, K.,Daly, L.,Wells, J.N.,Vuolo, L.,Mladenov, M.,Seda, M.,Jenkins, D.,Stephens, D.J.,Roberts, A.J.
Structure and tethering mechanism of dynein-2 intermediate chains in intraflagellar transport.
Embo J., 43:1257-1272, 2024

PubMed Abstract: Dynein-2 is a large multiprotein complex that powers retrograde intraflagellar transport (IFT) of cargoes within cilia/flagella, but the molecular mechanism underlying this function is still emerging. Distinctively, dynein-2 contains two identical force-generating heavy chains that interact with two different intermediate chains (WDR34 and WDR60). Here, we dissect regulation of dynein-2 function by WDR34 and WDR60 using an integrative approach including cryo-electron microscopy and CRISPR/Cas9-enabled cell biology. A 3.9 Å resolution structure shows how WDR34 and WDR60 use surprisingly different interactions to engage equivalent sites of the two heavy chains. We show that cilia can assemble in the absence of either WDR34 or WDR60 individually, but not both subunits. Dynein-2-dependent distribution of cargoes depends more strongly on WDR60, because the unique N-terminal extension of WDR60 facilitates dynein-2 targeting to cilia. Strikingly, this N-terminal extension can be transplanted onto WDR34 and retain function, suggesting it acts as a flexible tether to the IFT "trains" that assemble at the ciliary base. We discuss how use of unstructured tethers represents an emerging theme in IFT train interactions.

PubMed: 38454149
DOI: 10.1038/s44318-024-00060-1

Experimental method

X-RAY DIFFRACTION (2.02 Å)