PDBsum entry 4zdv

Protein transport

PDB id: 4zdv

Contents

Protein chain

126 a.a.

Waters ×116

PDB id:

4zdv

Name:

Protein transport

Title:

Crystal structure of lc3 in complex with fam134b lir

Structure:

Microtubule-associated proteins 1a/1b light chain 3a. Chain: a. Synonym: autophagy-related protein lc3 a,autophagy-related ubiquitin- like modifier lc3 a,map1 light chain 3-like protein 1,map1a/map1b light chain 3 a,map1a/map1b lc3 a,microtubule-associated protein 1 light chain 3 alpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: map1lc3a. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.80Å R-factor: 0.186 R-free: 0.223

Authors:

A.Khaminets,P.Grumati,I.Dikic,M.Akutsu

Key ref:

A.Khaminets et al. (2015). Regulation of endoplasmic reticulum turnover by selective autophagy. Nature, 522, 354-358. PubMed id: 26040720 DOI: 10.1038/nature14498

Date:

19-Apr-15 Release date: 03-Jun-15

Protein chain

Q9H492  (MLP3A_HUMAN) -  Microtubule-associated proteins 1A/1B light chain 3A from Homo sapiens

Seq: 121 a.a.

Struc: 126 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nature14498

Nature 522:354-358 (2015)

PubMed id: 26040720

Regulation of endoplasmic reticulum turnover by selective autophagy.

A.Khaminets, T.Heinrich, M.Mari, P.Grumati, A.K.Huebner, M.Akutsu, L.Liebmann, A.Stolz, S.Nietzsche, N.Koch, M.Mauthe, I.Katona, B.Qualmann, J.Weis, F.Reggiori, I.Kurth, C.A.Hübner, I.Dikic.

ABSTRACT

The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process. However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans.