5DN7

Crescerin uses a TOG domain array to regulate microtubules in the primary cilium

Summary for 5DN7

• Entry DOI: 10.2210/pdb5dn7/pdb
• Descriptor: Protein FAM179B (2 entities in total)
• Functional Keywords: tog domain, structural protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 32495.52

Authors

Das, A.,Dickinson, D.J.,Wood, C.C.,Goldstein, B.,Slep, K.C. (deposition date: 2015-09-09, release date: 2015-09-23, Last modification date: 2024-03-06)

Primary citation

Das, A.,Dickinson, D.J.,Wood, C.C.,Goldstein, B.,Slep, K.C.
Crescerin uses a TOG domain array to regulate microtubules in the primary cilium.
Mol.Biol.Cell, 26:4248-4264, 2015

PubMed Abstract: Eukaryotic cilia are cell-surface projections critical for sensing the extracellular environment. Defects in cilia structure and function result in a broad range of developmental and sensory disorders. However, mechanisms that regulate the microtubule (MT)-based scaffold forming the cilia core are poorly understood. TOG domain array-containing proteins ch-TOG and CLASP are key regulators of cytoplasmic MTs. Whether TOG array proteins also regulate ciliary MTs is unknown. Here we identify the conserved Crescerin protein family as a cilia-specific, TOG array-containing MT regulator. We present the crystal structure of mammalian Crescerin1 TOG2, revealing a canonical TOG fold with conserved tubulin-binding determinants. Crescerin1's TOG domains possess inherent MT-binding activity and promote MT polymerization in vitro. Using Cas9-triggered homologous recombination in Caenorhabditis elegans, we demonstrate that the worm Crescerin family member CHE-12 requires TOG domain-dependent tubulin-binding activity for sensory cilia development. Thus, Crescerin expands the TOG domain array-based MT regulatory paradigm beyond ch-TOG and CLASP, representing a distinct regulator of cilia structure.

PubMed: 26378256
DOI: 10.1091/mbc.E15-08-0603

Experimental method

X-RAY DIFFRACTION (2.2 Å)