Flexible and Extended Linker Domains Support Efficient Targeting of Heh2 to the Inner Nuclear Membrane

Irina L Rempel, Petra Popken, Ali Ghavami, Ankur Mishra, Rizqiya A Hapsari, Anouk H G Wolters, Annemiek C Veldsink, Marindy Klaassens, Anne C Meinema, Bert Poolman, Ben N G Giepmans, Patrick R Onck*, Anton Steen, Liesbeth M Veenhoff

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

Samenvatting

The nuclear pore complex (NPC) is embedded in the nuclear envelope and forms the main gateway to the nuclear interior including the inner nuclear membrane (INM). Two INM proteins in yeast are selectively imported. Their sorting signals consist of a nuclear localization signal, separated from the transmembrane domain by a long intrinsically disordered (ID) linker. We used computational models to predict the dynamic conformations of ID linkers and analyzed the INM targeting efficiency of proteins with linker regions with altered Stokes radii and decreased flexibilities. We find that flexibility, Stokes radius, and the frequency at which the linkers are at an extended end-to-end distance larger than 25 nm are good predictors for the targeting of the proteins. The data are consistent with a transport mechanism in which INM targeting of Heh2 is dependent on an ID linker that facilitates the crossing of the approximately 25-nm thick NPC scaffold.

Originele taal-2English
Pagina's (van-tot)185-195.e5
Aantal pagina's17
TijdschriftStructure
Volume28
Nummer van het tijdschrift2
Vroegere onlinedatum2-dec-2019
DOI's
StatusPublished - 4-feb-2020

Citeer dit