Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding

Structure. 2021 Jun 3;29(6):572-586.e6. doi: 10.1016/j.str.2021.01.001. Epub 2021 Feb 1.


The Parkin co-regulated gene protein (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.

Keywords: MEIG1; PACRG; PACRGL; Parkinson; axoneme; cilia; flagella; microtubule; sperm; tubulin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axoneme / metabolism
  • Binding Sites
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism*
  • Chlamydomonas reinhardtii / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Microscopy, Fluorescence
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Multiprotein Complexes / chemistry
  • Mutation
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Single Molecule Imaging
  • Tubulin / metabolism*


  • Cell Cycle Proteins
  • MEIG1 protein, human
  • Microfilament Proteins
  • Molecular Chaperones
  • Multiprotein Complexes
  • Nuclear Proteins
  • PACRG protein, human
  • Phosphoproteins
  • Tubulin