Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385519601> ?p ?o ?g. }
- W4385519601 abstract "Abstract Despite their lack of a defined 3D structure, intrinsically disordered regions (IDRs) of proteins play important biological roles. Many IDRs contain short linear motifs (SLiMs) that mediate protein-protein interactions (PPIs), which can be regulated by post-translational modifications like phosphorylation. 20% of pathogenic missense mutations are found in IDRs, and understanding how such mutations affect PPIs is essential for unraveling disease mechanisms. Here, we employed peptide-based interaction proteomics to investigate 36 disease-causing mutations affecting phosphorylation sites. Our results unveiled significant differences in interactomes between phosphorylated and non-phosphorylated peptides, often due to disrupted phosphorylation-dependent SLiMs. We focused on a mutation of a serine phosphorylation site in the transcription factor GATAD1, which causes dilated cardiomyopathy. We found that this phosphorylation site mediates interaction with 14-3-3 family proteins. Follow-up experiments revealed the structural basis of this interaction and suggest that 14-3-3 binding affects GATAD1 nucleocytoplasmic transport by masking a nuclear localisation signal. Our results demonstrate that pathogenic mutations of human phosphorylation sites can significantly impact protein-protein interactions, offering fresh insights into potential molecular mechanisms underlying pathogenesis." @default.
- W4385519601 created "2023-08-04" @default.
- W4385519601 creator A5001763350 @default.
- W4385519601 creator A5003644914 @default.
- W4385519601 creator A5027368560 @default.
- W4385519601 creator A5042532056 @default.
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- W4385519601 creator A5058400078 @default.
- W4385519601 creator A5059679748 @default.
- W4385519601 creator A5067074644 @default.
- W4385519601 date "2023-08-03" @default.
- W4385519601 modified "2023-10-02" @default.
- W4385519601 title "Pathogenic mutations of human phosphorylation sites affect protein-protein interactions" @default.
- W4385519601 cites W1517014083 @default.
- W4385519601 cites W1569018409 @default.
- W4385519601 cites W1934555946 @default.
- W4385519601 cites W1975121208 @default.
- W4385519601 cites W1988805210 @default.
- W4385519601 cites W1992983658 @default.
- W4385519601 cites W1994051305 @default.
- W4385519601 cites W1996868531 @default.
- W4385519601 cites W1998408165 @default.
- W4385519601 cites W2003236418 @default.
- W4385519601 cites W2006192061 @default.
- W4385519601 cites W2015115860 @default.
- W4385519601 cites W2022257442 @default.
- W4385519601 cites W2023333666 @default.
- W4385519601 cites W2038840577 @default.
- W4385519601 cites W2040452705 @default.
- W4385519601 cites W2041352318 @default.
- W4385519601 cites W2042655455 @default.
- W4385519601 cites W2043274355 @default.
- W4385519601 cites W2043581879 @default.
- W4385519601 cites W2050054339 @default.
- W4385519601 cites W2052889619 @default.
- W4385519601 cites W2071075259 @default.
- W4385519601 cites W2075517727 @default.
- W4385519601 cites W2080752012 @default.
- W4385519601 cites W2096358531 @default.
- W4385519601 cites W2098715150 @default.
- W4385519601 cites W2100407705 @default.
- W4385519601 cites W2104038552 @default.
- W4385519601 cites W2105016405 @default.
- W4385519601 cites W2105707485 @default.
- W4385519601 cites W2111607030 @default.
- W4385519601 cites W2116496305 @default.
- W4385519601 cites W2118971140 @default.
- W4385519601 cites W2121169682 @default.
- W4385519601 cites W2122772601 @default.
- W4385519601 cites W2124026197 @default.
- W4385519601 cites W2126177438 @default.
- W4385519601 cites W2133446638 @default.
- W4385519601 cites W2143407286 @default.
- W4385519601 cites W2154714625 @default.
- W4385519601 cites W2156407548 @default.
- W4385519601 cites W2159675211 @default.
- W4385519601 cites W2163341755 @default.
- W4385519601 cites W2164751765 @default.
- W4385519601 cites W2167279371 @default.
- W4385519601 cites W2171347864 @default.
- W4385519601 cites W2256016639 @default.
- W4385519601 cites W2266690852 @default.
- W4385519601 cites W2289821466 @default.
- W4385519601 cites W2298224298 @default.
- W4385519601 cites W2300545781 @default.
- W4385519601 cites W2621386467 @default.
- W4385519601 cites W2780166259 @default.
- W4385519601 cites W2793216206 @default.
- W4385519601 cites W2800613882 @default.
- W4385519601 cites W2806040128 @default.
- W4385519601 cites W2807814263 @default.
- W4385519601 cites W2891583395 @default.
- W4385519601 cites W2891753225 @default.
- W4385519601 cites W2901154392 @default.
- W4385519601 cites W2912126500 @default.
- W4385519601 cites W2912820434 @default.
- W4385519601 cites W2921921533 @default.
- W4385519601 cites W2959620165 @default.
- W4385519601 cites W2977723521 @default.
- W4385519601 cites W2999515714 @default.
- W4385519601 cites W3005045932 @default.
- W4385519601 cites W3005901855 @default.
- W4385519601 cites W3019507822 @default.
- W4385519601 cites W3036355682 @default.
- W4385519601 cites W3042135946 @default.
- W4385519601 cites W3045402435 @default.
- W4385519601 cites W3048753716 @default.
- W4385519601 cites W3119506213 @default.
- W4385519601 cites W3135014513 @default.
- W4385519601 cites W3138817412 @default.
- W4385519601 cites W3159731292 @default.
- W4385519601 cites W3159915352 @default.
- W4385519601 cites W3168631962 @default.
- W4385519601 cites W3192210502 @default.
- W4385519601 cites W4210398894 @default.
- W4385519601 cites W4221003075 @default.
- W4385519601 cites W4223510002 @default.
- W4385519601 cites W4223623159 @default.
- W4385519601 cites W4224101418 @default.