Positive zip coding in small protein translocation

Yukari Okamoto,Sojin Shikano

doi:10.1074/jbc.h118.001415

Abstract

Most newly synthesized proteins destined for the secretory pathway contain a signal peptide (SP) that triggers cotranslational translocation into the endoplasmic reticulum (ER). However, how small polypeptides undergo ER translocation is not fully understood. In this issue of JBC, Guo et al. describe a mechanism for posttranslational translocation of small secretory proteins featuring a positive charge within the SP N-terminal region. Defects in this element disrupt proper secretion and explain the effects of genetic mutations associated with one type of diabetes.

Highlights

Proteins directed to the secretory pathway can be secreted from the cell or targeted to various membrane compartments, including the endoplasmic reticulum (ER)[2]; nearly 40% of human proteins are predicted to go through this pathway (1)
signal peptide (SP) are recognized by the signal recognition particle (SRP), whereas chain elongation is still ongoing on the ribosome
Guo and colleagues (9) had previously found one clue to this mystery: In studying the R6C and R6H preproinsulin mutations associated with maturity onset diabetes of youth (MODY), they observed that these constructs were not fully translocated and that the untranslocated preproinsulin proteins remained associated with the ER membrane and accumulated intracellularly, which promoted ␤-cell death

Summary

Introduction

Proteins directed to the secretory pathway can be secreted from the cell or targeted to various membrane compartments, including the endoplasmic reticulum (ER)[2]; nearly 40% of human proteins are predicted to go through this pathway (1). Of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S. Ashland Ave., MBRB 2002, Chicago, IL 60607. Secretory proteins commonly bear SPs at their N terminus, which typically contain a stretch of hydrophobic residues that may be preceded by one or two positively charged residues called the n-region (8).

Results

Conclusion