?

Subcellular localization

cilia, flagella, Nucleoplasm, Vesicles

Functional category

• Metabolism
• Motile cilium & axoneme
• Non-motile cilium / primary cilium
• Ciliary assembly/disassembly
• Cilia–cytoskeleton/adhesion links

Function

The Parkin Co-Regulated Gene (PACRG) binds at the inner junction between doublet microtubules of the axoneme, a structure found in flagella and cilia. PACRG binds to the adaptor protein meiosis expressed gene 1 (MEIG1), but how they bind to microtubules is unknown. Here, we report the crystal structure of human PACRG in complex with MEIG1. PACRG adopts a helical repeat fold with a loop that interacts with MEIG1. Using the structure of the axonemal doublet microtubule from the protozoan Chlamydomonas reinhardtii and single-molecule fluorescence microscopy, we propose that PACRG binds to microtubules while simultaneously recruiting free tubulin to catalyze formation of the inner junction. We show that the homologous PACRG-like protein also mediates dual tubulin interactions but does not bind MEIG1. Our findings establish a framework to assess the function of the PACRG family of proteins and MEIG1 in regulating axoneme assembly. Khan et al. solved the crystal structure of human PACRG:MEIG1, a protein complex essential for flagella maturation in sperm. PACRG and its homolog PACRGL can recruit tubulin to microtubules via multiple binding sites, suggesting a mechanism for formation of the axonemal doublet microtubule found in flagella and cilia(33529594).