7WEK

Crystal structure of the mouse Wdr47 NTD in complex with the WBR motif form Camsap3.

Summary for 7WEK

• Entry DOI: 10.2210/pdb7wek/pdb
• Descriptor: WD repeat-containing protein 47, WBR motif form Calmodulin-regulated spectrin-associated protein 3 (2 entities in total)
• Functional Keywords: lish motif containing protein, protein binding
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 73533.09

Authors

Ren, J.Q.,Li, D.,Feng, W. (deposition date: 2021-12-23, release date: 2022-11-30, Last modification date: 2023-11-29)

Primary citation

Ren, J.,Li, D.,Liu, J.,Liu, H.,Yan, X.,Zhu, X.,Feng, W.
Intertwined Wdr47-NTD dimer recognizes a basic-helical motif in Camsap proteins for proper central-pair microtubule formation.
Cell Rep, 41:111589-111589, 2022

PubMed Abstract: Calmodulin-regulated spectrin-associated proteins (Camsaps) bind to the N-terminal domain of WD40-repeat 47 (Wdr47-NTD; featured with a LisH-CTLH motif) to properly generate axonemal central-pair microtubules (CP-MTs) for the planar beat pattern of mammalian motile multicilia. The underlying molecular mechanism, however, remains unclear. Here, we determine the structures of apo-Wdr47-NTD and Wdr47-NTD in complex with a characteristic Wdr47-binding region (WBR) from Camsap3. Wdr47-NTD forms an intertwined dimer with a special cross-over region (COR) in addition to the canonical LisH and globular α-helical core (GAC). The basic WBR peptide adopts an α-helical conformation and anchors to a tailored acidic pocket embedded in the COR. Mutations in this target-binding pocket disrupt the interaction between Wdr47-NTD and Camsap3. Impairing Wdr47-Camsap interactions markedly reduces rescue effects of Wdr47 on CP-MTs and ciliary beat of Wdr47-deficient ependymal cells. Thus, Wdr47-NTD functions by recognizing a specific basic helical motif in Camsap proteins via its non-canonical COR, a target-binding site in LisH-CTLH-containing domains.

PubMed: 36351391
DOI: 10.1016/j.celrep.2022.111589

Experimental method

X-RAY DIFFRACTION (3.21 Å)