FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2802525918> ?p ?o ?g. }

• W2802525918 endingPage "1129" @default.
• W2802525918 startingPage "1114" @default.
• W2802525918 abstract "Nuclear import involves the recognition by importin (IMP) superfamily members of nuclear localization signals (NLSs) within protein cargoes destined for the nucleus, the best understood being recognition of classical NLSs (cNLSs) by the IMPα/β1 heterodimer. Although the cNLS consensus [K-(K/R)-X-(K/R) for positions P2-P5] is generally accepted, recent studies indicated that the contribution made by different residues at the P4 position can vary. Here, we apply a combination of microscopy, molecular dynamics, crystallography, in vitro binding, and bioinformatics approaches to show that the nature of residues at P4 indeed modulates cNLS function in the context of a prototypical Simian Virus 40 large tumor antigen-derived cNLS (KKRK, P2-5). Indeed, all hydrophobic substitutions in place of R impaired binding to IMPα and nuclear targeting, with the largest effect exerted by a G residue at P4. Substitution of R with neutral hydrophobic residues caused the loss of electrostatic and van der Waals interactions between the P4 residue side chains and IMPα. Detailed bioinformatics analysis confirmed the importance of the P4 residue for cNLS function across the human proteome, with specific residues such as G being associated with low activity. Furthermore, we validate our findings for two additional cNLSs from human cytomegalovirus (HCMV) DNA polymerase catalytic subunit UL54 and processivity factor UL44, where a G residue at P4 results in a 2-3-fold decrease in NLS activity. Our results thus showed that the P4 residue makes a hitherto poorly appreciated contribution to nuclear import efficiency, which is essential to determining the precise nuclear levels of cargoes." @default.
• W2802525918 created "2018-05-17" @default.
• W2802525918 creator A5006689011 @default.
• W2802525918 creator A5007745751 @default.
• W2802525918 creator A5013496328 @default.
• W2802525918 creator A5015687995 @default.
• W2802525918 creator A5019921720 @default.
• W2802525918 creator A5025037333 @default.
• W2802525918 creator A5029725982 @default.
• W2802525918 creator A5053527976 @default.
• W2802525918 creator A5070182251 @default.
• W2802525918 creator A5074040623 @default.
• W2802525918 creator A5083575743 @default.
• W2802525918 creator A5091348755 @default.
• W2802525918 date "2018-08-01" @default.
• W2802525918 modified "2023-10-16" @default.
• W2802525918 title "Contribution of the residue at position 4 within classical nuclear localization signals to modulating interaction with importins and nuclear targeting" @default.
• W2802525918 cites W1550199886 @default.
• W2802525918 cites W1576998218 @default.
• W2802525918 cites W1770339820 @default.
• W2802525918 cites W1941075377 @default.
• W2802525918 cites W1966078827 @default.
• W2802525918 cites W1970170124 @default.
• W2802525918 cites W1976499671 @default.
• W2802525918 cites W1976572901 @default.
• W2802525918 cites W1982941652 @default.
• W2802525918 cites W1985191382 @default.
• W2802525918 cites W1986045651 @default.
• W2802525918 cites W1988808584 @default.
• W2802525918 cites W1989700964 @default.
• W2802525918 cites W1992920020 @default.
• W2802525918 cites W1995160911 @default.
• W2802525918 cites W1997565725 @default.
• W2802525918 cites W1998528794 @default.
• W2802525918 cites W2001584156 @default.
• W2802525918 cites W2003847336 @default.
• W2802525918 cites W2009815491 @default.
• W2802525918 cites W2011797148 @default.
• W2802525918 cites W2017835622 @default.
• W2802525918 cites W2018563196 @default.
• W2802525918 cites W2020828286 @default.
• W2802525918 cites W2027408247 @default.
• W2802525918 cites W2033722975 @default.
• W2802525918 cites W2035503835 @default.
• W2802525918 cites W2035687084 @default.
• W2802525918 cites W2038758364 @default.
• W2802525918 cites W2040420691 @default.
• W2802525918 cites W2042487912 @default.
• W2802525918 cites W2043929240 @default.
• W2802525918 cites W2046037976 @default.
• W2802525918 cites W2048658657 @default.
• W2802525918 cites W2049132410 @default.
• W2802525918 cites W2051665782 @default.
• W2802525918 cites W2053796273 @default.
• W2802525918 cites W2065148518 @default.
• W2802525918 cites W2067099248 @default.
• W2802525918 cites W2069512161 @default.
• W2802525918 cites W2076984362 @default.
• W2802525918 cites W2079433334 @default.
• W2802525918 cites W2082389145 @default.
• W2802525918 cites W2083392791 @default.
• W2802525918 cites W2089084279 @default.
• W2802525918 cites W2089610358 @default.
• W2802525918 cites W2097239500 @default.
• W2802525918 cites W2097432163 @default.
• W2802525918 cites W2102801630 @default.
• W2802525918 cites W2106246537 @default.
• W2802525918 cites W2110808180 @default.
• W2802525918 cites W2125079066 @default.
• W2802525918 cites W2126203424 @default.
• W2802525918 cites W2127892739 @default.
• W2802525918 cites W2132172347 @default.
• W2802525918 cites W2132629607 @default.
• W2802525918 cites W2135428633 @default.
• W2802525918 cites W2138740433 @default.
• W2802525918 cites W2144081223 @default.
• W2802525918 cites W2144151973 @default.
• W2802525918 cites W2147949826 @default.
• W2802525918 cites W2150981663 @default.
• W2802525918 cites W2151273144 @default.
• W2802525918 cites W2156891333 @default.
• W2802525918 cites W2158125183 @default.
• W2802525918 cites W2163341755 @default.
• W2802525918 cites W2165779834 @default.
• W2802525918 cites W2166498431 @default.
• W2802525918 cites W2180229411 @default.
• W2802525918 cites W2584459311 @default.
• W2802525918 cites W2747798162 @default.
• W2802525918 cites W2793420120 @default.
• W2802525918 cites W2795145547 @default.
• W2802525918 cites W4242267726 @default.
• W2802525918 doi "https://doi.org/10.1016/j.bbamcr.2018.05.006" @default.
• W2802525918 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29750988" @default.
• W2802525918 hasPublicationYear "2018" @default.
• W2802525918 type Work @default.
• W2802525918 sameAs 2802525918 @default.
• W2802525918 citedByCount "20" @default.
• W2802525918 countsByYear W28025259182018 @default.

• next