Map · Cell biology · Autophagy

Autophagy LC3 lipidation · membrane tag

When the cell eats part of itself, it first needs a membrane tag. A ubiquitin-like cascade ligates LC3 onto the lipid PE — the same activate→conjugate logic as ubiquitin, but the acceptor is a membrane lipid. Layer 2 of three — pick a machine. Real crystal coordinates (RCSB PDB).

The four machines

PROTEASE · PRIME

ATG4B (LC3-processing protease)

pro-LC3 + H₂O → LC3-I

First the LC3 precursor is trimmed: ATG4B is a cysteine protease that exposes the C-terminal glycine the cascade needs.

EC 3.4.22 · PDB 2Z0D

▶ OPEN SIMULATOR
→
LC3-I
E1-LIKE · ACTIVATE

ATG7 (E1-like activating enzyme)

Atg8 + ATP → E1~Atg8 + AMP + PPᵢ

Activates LC3/Atg8 with ATP and hands it on as a thioester — the same activation step UBA1 performs for ubiquitin.

E1-like · PDB 3VH4

▶ OPEN SIMULATOR
→
E1~LC3
E2-LIKE · CONJUGATE

ATG3 (E2-like conjugating enzyme)

E1~LC3 + ATG3 → ATG3~LC3

Receives LC3 from ATG7 and passes it toward the lipid. The E2-like relay of the cascade; a trans-thioesterification.

EC 2.3.2 · PDB 9E8P

▶ OPEN SIMULATOR
→
ATG3~LC3
E3-LIKE · LIGATE

ATG12–ATG5 (conjugate)

presents LC3 to the lipid PE

Acts like an E3: brings LC3 next to the membrane lipid PE so it can be ligated on. The resulting LC3-PE anchors the autophagosome.

E3-like · PDB 4GDL

▶ OPEN SIMULATOR
⤷ A ubiquitin-like cascade aimed at a lipid: ATG4B primes LC3, ATG7 activates, ATG3 relays, and ATG12–ATG5 ligates it onto PE.