DAW1

Model summary

A cytosolic beta-propeller scaffold that concentrates at centrosomes and basal bodies to coordinate cilium biogenesis. By using a WD40 repeat platform, it binds multiple partners to organize intraflagellar transport and to chaperone assembly of axonemal dynein arms. This multivalent interaction surface enables the timely assembly and delivery of structural and motor components required for cilium assembly and maintenance.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture, which is dominated by WD40 beta-propeller modules.

   IPR001680 (WD40 repeat, residues 81–415) spans almost the entire protein and is reinforced by multiple WD40/YVTN repeat-like superfamily signatures: IPR015943 (WD40/YVTN repeat-like-containing domain superfamily) appears four times in a contiguous block from residues 86–415, consistent with a multi-bladed beta-propeller scaffold. The WD40-repeat core is further specified by conserved sites and subclass markers: IPR019775 (WD40 repeat, conserved site) occurs at residues 192–206, 234–248, 276–290, and 360–374, while IPR020472 (PAC1/LIS1-like, WD-40 repeat) marks repeats at residues 192–206 and 360–374. The ordered array of WD repeats and conserved sites indicates a rigid, solvent-exposed beta-propeller platform optimized for multivalent protein–protein interactions rather than catalysis. This architecture causally supports GO:0005515 protein binding as the primary molecular function: WD40 propellers create composite binding grooves that nucleate and stabilize large macromolecular assemblies.

2. 02

   From this scaffolded binding capacity, I infer roles in transport and assembly pathways that require precise multiprotein coordination.

   The explicit coupling of WD40 repeats to dynein-associated pathways is suggested by the localization and process annotations. A WD40 scaffold situated at centrosomes and basal bodies can organize cargo adaptors and motors that drive intraflagellar transport; this directly supports GO:0042073 intraciliary transport. The same scaffold can chaperone and assemble axonemal dynein complexes by stabilizing intermediate subunits and docking them onto assembly factors, aligning with GO:0036158 outer dynein arm assembly. By orchestrating both intraciliary trafficking and dynein arm maturation, the scaffold contributes to GO:0060271 cilium assembly, providing a coherent causal chain from binding architecture to ciliary biogenesis.

3. 03

   Cellular localization follows from where such scaffolding is required.

   The beta-propeller platform is soluble and cytosolic, consistent with GO:0005829 cytosol, but it concentrates at microtubule-organizing structures that seed and maintain cilia. Its assembly function predicts accumulation at the GO:0036064 ciliary basal body and the GO:0005813 centrosome, where dynein preassembly and IFT initiation are coordinated. The stated subcellular distribution—cytoplasm/cytoskeleton and specifically centrosomes and basal bodies—matches this mechanistic placement.

4. 04

   Mechanistically, I propose that the WD40 propeller forms a hub that recruits IFT-B and IFT-A subcomplexes and dynein assembly factors at the basal body, stabilizing cargo adaptors and promoting handoff between cytoplasmic preassembly and axonemal incorporation.

   Likely partners include IFT-B core components (e.g., IFT88 and IFT52) that ferry axonemal precursors, dynein assembly factors (DNAAF family) that mature outer dynein arms, and centrosomal scaffolds (CEP proteins) that anchor the complex. Through these interactions, the scaffold times intraciliary transport with dynein arm assembly to ensure efficient cilium assembly and maintenance.