Mechanism of Quality Control of Nascent Membrane Proteins

Abstract

Membrane proteins consist of nearly 20% of human proteome and perform a variety of essential functions for cell physiology. It is estimated that ~5000 membrane proteins are synthesized and inserted into the membrane at the endoplasmic reticulum (ER). Folding and maturation of nascent membrane proteins are complex and error-prone processes. Membrane proteins failed to properly fold and assemble are eliminated by a quality control process termed ER-associated degradation (ERAD) pathway. During ERAD, membrane proteins are recognized, modified with ubiquitin chain, extracted from the membrane, and finally degraded by the cytoplasmic 26S proteasome. The ERAD pathway targets majority of non-native proteins as well as some regulatory proteins in many cellular compartments, including ER lumen, ER membrane and nuclear membrane. Here, I review the protein degradation machineries and key steps involved in membrane protein degradation from the ER.