Structural and functional analysis of Hikeshi, a new nuclear transport receptor of Hsp70s

Acta Crystallographica. Section D, Biological Crystallography
Jinsue SongS J Lee

Abstract

Hikeshi is a nuclear transport receptor required for cell survival after stress. It mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins (Hsp70s) through interactions with FG-nucleoporins (FG-Nups), which are proteins in nuclear pore complexes (NPCs). Here, the crystal structure of human Hikeshi is presented at 1.8 Å resolution. Hikeshi forms an asymmetric homodimer that is responsible for the interaction with Hsp70s. The asymmetry of Hikeshi arises from the distinct conformation of the C-terminal domain (CTD) and the flexibility of the linker regions of each monomer. Structure-guided mutational analyses showed that both the flexible linker region and the CTD are important for nuclear import of Hsp70. Pull-down assays revealed that only full-length Hsp70s can interact with Hikeshi. The N-terminal domain (NTD) consists of a jelly-roll/β-sandwich fold structure which contains hydrophobic pockets involved in FG-Nup recognition. A unique extended loop (E-loop) in the NTD is likely to regulate the interactions of Hikeshi with FG-Nups. The crystal structure of Hikeshi explains how Hikeshi participates in the regulation of nuclear import through the recognition of FG-Nups and which part of Hikeshi affects its bindi...Continue Reading

References

Jan 1, 1991·Annual Review of Biochemistry·R J Ellis, S M van der Vies
Nov 1, 1990·Trends in Biochemical Sciences·M SarasteA Wittinghofer
Nov 6, 1986·Nature·D I StuartD C Phillips
Jan 5, 1981·Journal of Molecular Biology·C ChothiaD Richardson
Jan 5, 1993·Journal of Molecular Biology·G D Van DuyneJ Clardy
Feb 21, 1998·Nucleic Acids Research·L Holm, C Sander
Jul 21, 1998·Annals of the New York Academy of Sciences·A Mathew, R I Morimoto
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·W C SuhC A Gross
Dec 28, 1999·Annual Review of Cell and Developmental Biology·D Görlich, U Kutay
Feb 23, 2000·The Journal of Cell Biology·M P RoutB T Chait
Jun 18, 2002·The EMBO Journal·Richard BaylissMurray Stewart
Aug 28, 2002·The Journal of Cell Biology·Janet M CronshawMichael J Matunis
Oct 10, 2002·The Journal of Biological Chemistry·Richard BaylissMurray Stewart
Feb 13, 2003·Journal of Molecular Biology·Richard P GrantMurray Stewart
Oct 1, 1994·Trends in Cell Biology·M P Rout, S R Wente
May 8, 2004·Trends in Plant Science·Wangxia WangArie Altman
May 19, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Maiko FurutaNaoko Imamoto
Sep 16, 2004·Journal of Cell Science·Xian-Chun ZengEvan Eisenberg
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jun 17, 2006·Cell·Elizabeth J Tran, Susan R Wente
Feb 9, 2007·Nature Reviews. Molecular Cell Biology·Murray Stewart
May 18, 2007·Annual Review of Biochemistry·Atlanta CookElena Conti
Jun 23, 2007·Nucleic Acids Research·K G TinaN Srinivasan
Sep 19, 2007·The Journal of Cell Biology·Laura J Terry, Susan R Wente
Jan 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Walid AwadLinda M Hendershot
Jun 14, 2008·Molecular Cell·Jonathan P SchuermannRui Sousa
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Jul 24, 2010·Nature Reviews. Molecular Cell Biology·Harm H Kampinga, Elizabeth A Craig
Aug 14, 2010·Molecular Cell·Matthias P Mayer
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Aug 9, 2011·Nature Structural & Molecular Biology·Marianna TeplovaDinshaw J Patel
Oct 4, 2011·Biophysical Journal·Sigrid Milles, Edward A Lemke
Feb 9, 2012·Physical Biology·Aris SklirosRobert L Jernigan
May 26, 2012·PloS One·Lakshmipuram Seshadri SwapnaNarayanaswamy Srinivasan
May 28, 2013·Nature Structural & Molecular Biology·Ruifeng QiQinglian Liu

❮ Previous
Next ❯

Citations

Nov 3, 2015·Journal of Molecular Biology·Mary ChristieBostjan Kobe
Dec 22, 2016·European Journal of Human Genetics : EJHG·Catalina VasilescuChristopher J Carroll
Oct 6, 2017·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Khondoker Md Zulfiker RahmanNaoko Imamoto

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.