PDBsum entry 4gdk

Protein binding

PDB id: 4gdk

Contents

Protein chains

88 a.a.

267 a.a.

34 a.a.

35 a.a.

Metals

_NA ×2

Waters ×76

PDB id:

4gdk

Name:

Protein binding

Title:

Crystal structure of human atg12~atg5 conjugate in complex with an n- terminal fragment of atg16l1

Structure:

Ubiquitin-like protein atg12. Chain: a, d. Synonym: autophagy-related protein 12, apg12-like. Engineered: yes. Autophagy protein 5. Chain: b, e. Synonym: apg5-like, apoptosis-specific protein. Engineered: yes. Autophagy-related protein 16-1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: apg12, apg12l, atg12. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: apg5l, asp, atg5. Gene: apg16l, atg16l1, unq9393/pro34307.

Resolution:

2.70Å R-factor: 0.180 R-free: 0.236

Authors:

C.Otomo,Z.Metlagel,G.Takaesu,T.Otomo

Key ref:

C.Otomo et al. (2013). Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat Struct Biol, 20, 59-66. PubMed id: 23202584

Date:

31-Jul-12 Release date: 05-Dec-12

Protein chains

O94817  (ATG12_HUMAN) -  Ubiquitin-like protein ATG12 from Homo sapiens

Seq: 140 a.a.

Struc: 88 a.a.

Protein chains

Q9H1Y0  (ATG5_HUMAN) -  Autophagy protein 5 from Homo sapiens

Seq: 275 a.a.

Struc: 267 a.a.

Protein chain

Q676U5  (A16L1_HUMAN) -  Autophagy-related protein 16-1 from Homo sapiens

Seq: 607 a.a.

Struc: 34 a.a.*

Protein chain

Q676U5  (A16L1_HUMAN) -  Autophagy-related protein 16-1 from Homo sapiens

Seq: 607 a.a.

Struc: 35 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Nat Struct Biol 20:59-66 (2013)

PubMed id: 23202584

Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy.

C.Otomo, Z.Metlagel, G.Takaesu, T.Otomo.

ABSTRACT

The autophagy factor ATG12~ATG5 conjugate exhibits E3 ligase-like activity which facilitates the lipidation of members of the LC3 family. The crystal structure of the human ATG12~ATG5 conjugate bound to the N-terminal region of ATG16L1, the factor that recruits the conjugate to autophagosomal membranes, reveals an integrated architecture in which ATG12 docks onto ATG5 through conserved residues. ATG12 and ATG5 are oriented such that other conserved residues on each molecule, including the conjugation junction, form a continuous surface patch. Mutagenesis data support the importance of both the interface between ATG12 and ATG5 and the continuous patch for E3 activity. The ATG12~ATG5 conjugate interacts with the E2 enzyme ATG3 with high affinity through another surface location that is exclusive to ATG12, suggesting a different role of the continuous patch in E3 activity. These findings provide a foundation for understanding the mechanism of LC3 lipidation.