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Nuclear export of phosphorylated proteins by Karyopherin MSN5


EMSL Project ID
51771

Abstract

MSN5 is the 142 kDa S. cerevisiae exportin, which exports many different protein cargoes from the nucleus to the cytoplasm in response to cellular environmental changes. Peptide signals in several cargoes that bind MSN5 have been mapped but their diverse sequences do not inform on key features of the nuclear export signals (NESs) or how MSN5 recognizes them. At this time, the only known NES is the leucine-rich NES that is recognized by the general exportin CRM1. This proposal, which focuses on structural determination of MSN5 in complex with its phosphorylated cargoes, describes an opportunity to uncover a new class of NES. Additionally, the mammalian homolog of MSN5, XPO5, is an exportin that exports double stranded RNA such as pre-microRNAs. Comparison of MSN5 structures with already available XPO5-RNA-RanGTP structures will reveal determinants of cargo specificity in the two homologous systems and possibly uncover novel protein cargoes for XPO5.

Project Details

Start Date
2020-12-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Yuh Chook
Institution
University of Texas Southwestern Medical Center

Team Members

Ho Yee Joyce Fung
Institution
University of Texas Southwestern Medical Center

Yang Li
Institution
University of Texas Southwestern Medical Center

Zhe Chen
Institution
University of Texas Southwestern Medical Center

Jenny Jiou
Institution
University of Texas Southwestern Medical Center

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory