Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains

J Biol Chem. 2005 Jul 1;280(26):24610-7. doi: 10.1074/jbc.M413565200. Epub 2005 Apr 27.

Abstract

Microtubule-associated protein (MAP) light chain 3 (LC3) is a human homologue of yeast Apg8/Aut7/Cvt5 (Atg8), which is essential for autophagy. MAP-LC3 is cleaved by a cysteine protease to produce LC3-I, which is located in cytosolic fraction. LC3-I, in turn, is converted to LC3-II through the actions of E1- and E2-like enzymes. LC3-II is covalently attached to phosphatidylethanolamine on its C terminus, and it binds tightly to autophagosome membranes. We determined the solution structure of LC3-I and found that it is divided into N- and C-terminal subdomains. Additional analysis using a photochemically induced dynamic nuclear polarization technique also showed that the N-terminal subdomain of LC3-I makes contact with the surface of the C-terminal subdomain and that LC3-I adopts a single compact conformation in solution. Moreover, the addition of dodecylphosphocholine into the LC3-I solution induced chemical shift perturbations primarily in the C-terminal subdomain, which implies that the two subdomains have different sensitivities to dodecylphosphocholine micelles. On the other hand, deletion of the N-terminal subdomain abolished binding of tubulin and microtubules. Thus, we showed that two subdomains of the LC3-I structure have distinct functions, suggesting that MAP-LC3 can act as an adaptor protein between microtubules and autophagosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy
  • Cysteine / chemistry
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Escherichia coli / metabolism
  • Gene Deletion
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microtubule-Associated Proteins / chemistry*
  • Microtubules / chemistry
  • Models, Molecular
  • Mutation
  • Phagocytosis
  • Phosphatidylethanolamines / chemistry
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemistry
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Surface Plasmon Resonance

Substances

  • MAP1LC3A protein, human
  • MAP1LC3B protein, human
  • MAP1LC3C protein, human
  • Microtubule-Associated Proteins
  • Phosphatidylethanolamines
  • Recombinant Proteins
  • Phosphorylcholine
  • phosphatidylethanolamine
  • dodecylphosphocholine
  • Cysteine

Associated data

  • PDB/1V49