2023
DOI: 10.1101/2023.11.02.565367
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The intrinsically disordered transcriptional activation domain of CIITA is functionally tuneable by single substitutions: An exception or a new paradigm?

Shwetha Sreenivasan,
Paul Heffren,
Kyung-Shin Suh
et al.

Abstract: During protein evolution, some amino acid substitutions modulate protein function (“tuneability”). In most proteins, the tuneable range is wide and can be sampled by a set of protein variants that each contains multiple amino acid substitutions. In other proteins, the full tuneable range can be accessed by a set of variants that each contains a single substitution. Indeed, in some globular proteins, the full tuneable range can be accessed by the set of site-saturating substitutions at an individual “rheostat” … Show more

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Cited by 1 publication
(5 citation statements)
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“…Third, of the ZmPYK positions tested, none were rheostat positions; instead, the substitution variants at many positions were evenly split between those with WT-like affinity and those that were inactive (Page et al, 2022). This novel substitution phenotype (named "WT/inactive split") was not previously observed in any of our prior studies investigating substitutions in nine natural and eight engineered proteins (Fenton et al, 2020(Fenton et al, , 2022Hodges et al, 2018;Martin et al, 2020;Meinhardt et al, 2013;Ruggiero et al, 2021Ruggiero et al, , 2022Sousa et al, 2016;Sreenivasan et al, 2024;Swint-Kruse et al, 2021Swint-Kruse & Fenton, 2024;Wu et al, 2019).…”
Section: Possible Origins Of the Wt/inactive Split Phenotypementioning
confidence: 64%
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“…Third, of the ZmPYK positions tested, none were rheostat positions; instead, the substitution variants at many positions were evenly split between those with WT-like affinity and those that were inactive (Page et al, 2022). This novel substitution phenotype (named "WT/inactive split") was not previously observed in any of our prior studies investigating substitutions in nine natural and eight engineered proteins (Fenton et al, 2020(Fenton et al, , 2022Hodges et al, 2018;Martin et al, 2020;Meinhardt et al, 2013;Ruggiero et al, 2021Ruggiero et al, , 2022Sousa et al, 2016;Sreenivasan et al, 2024;Swint-Kruse et al, 2021Swint-Kruse & Fenton, 2024;Wu et al, 2019).…”
Section: Possible Origins Of the Wt/inactive Split Phenotypementioning
confidence: 64%
“…However, in experiments, none of the predicted ZmPYK positions showed rheostatic outcomes for K app-PEP (Page et al, 2022). Furthermore, the substitution phenotypes for nine positions did not align with any of the previously-observed phenotypes (rheostat, neutral, or toggle) (Campitelli et al, 2021;Fenton et al, 2020Fenton et al, , 2022Hodges et al, 2018;Martin et al, 2020;Meinhardt et al, 2013;Miller et al, 2017;Ruggiero et al, 2021Ruggiero et al, , 2022Sreenivasan et al, 2024;Swint-Kruse, 2016;Swint-Kruse et al, 2021Swint-Kruse & Fenton, 2024;Wu et al, 2019). Instead, substitutions at these positions were almost evenly split between wild-type-like and inactive substitution variants (the "WT/inactive split" phenotype).…”
Section: Introductionmentioning
confidence: 85%
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