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- W4200295183 abstract "Protein domains are the basic units of protein structure and function. Comparative analysis of genomes and proteomes showed that domain recombination is a main driver of multidomain protein functional diversification and some of the constraining genomic mechanisms are known. Much less is known about biophysical mechanisms that determine whether protein domains can be combined into viable protein folds. Here, we use massively parallel insertional mutagenesis to determine compatibility of over 300,000 domain recombination variants of the Inward Rectifier K+ channel Kir2.1 with channel surface expression. Our data suggest that genomic and biophysical mechanisms acted in concert to favor gain of large, structured domain at protein termini during ion channel evolution. We use machine learning to build a quantitative biophysical model of domain compatibility in Kir2.1 that allows us to derive rudimentary rules for designing domain insertion variants that fold and traffic to the cell surface. Positional Kir2.1 responses to motif insertion clusters into distinct groups that correspond to contiguous structural regions of the channel with distinct biophysical properties tuned towards providing either folding stability or gating transitions. This suggests that insertional profiling is a high-throughput method to annotate function of ion channel structural regions." @default.
- W4200295183 created "2021-12-31" @default.
- W4200295183 creator A5000189657 @default.
- W4200295183 creator A5000600591 @default.
- W4200295183 creator A5020072810 @default.
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- W4200295183 creator A5078693340 @default.
- W4200295183 creator A5086631720 @default.
- W4200295183 creator A5091262014 @default.
- W4200295183 date "2021-12-08" @default.
- W4200295183 modified "2023-10-17" @default.
- W4200295183 title "Probing ion channel functional architecture and domain recombination compatibility by massively parallel domain insertion profiling" @default.
- W4200295183 cites W1514384576 @default.
- W4200295183 cites W1518056784 @default.
- W4200295183 cites W1581315874 @default.
- W4200295183 cites W1967214752 @default.
- W4200295183 cites W1969129798 @default.
- W4200295183 cites W1969644422 @default.
- W4200295183 cites W1972177221 @default.
- W4200295183 cites W1973491891 @default.
- W4200295183 cites W1975680413 @default.
- W4200295183 cites W1977516605 @default.
- W4200295183 cites W1983399409 @default.
- W4200295183 cites W1986347357 @default.
- W4200295183 cites W1990622714 @default.
- W4200295183 cites W1993496775 @default.
- W4200295183 cites W1993506738 @default.
- W4200295183 cites W1995375772 @default.
- W4200295183 cites W2001831734 @default.
- W4200295183 cites W2007085691 @default.
- W4200295183 cites W2007808117 @default.
- W4200295183 cites W2011398679 @default.
- W4200295183 cites W2012651793 @default.
- W4200295183 cites W2013726100 @default.
- W4200295183 cites W2016555254 @default.
- W4200295183 cites W2020652110 @default.
- W4200295183 cites W2021520922 @default.
- W4200295183 cites W2027542725 @default.
- W4200295183 cites W2027711565 @default.
- W4200295183 cites W2027891522 @default.
- W4200295183 cites W2031447561 @default.
- W4200295183 cites W2035689996 @default.
- W4200295183 cites W2043833442 @default.
- W4200295183 cites W2044476679 @default.
- W4200295183 cites W2046535373 @default.
- W4200295183 cites W2050140768 @default.
- W4200295183 cites W2053937911 @default.
- W4200295183 cites W2058276503 @default.
- W4200295183 cites W2058309529 @default.
- W4200295183 cites W2059206109 @default.
- W4200295183 cites W2060588922 @default.
- W4200295183 cites W2063252182 @default.
- W4200295183 cites W2076502650 @default.
- W4200295183 cites W2080434522 @default.
- W4200295183 cites W2080643147 @default.
- W4200295183 cites W2085497102 @default.
- W4200295183 cites W2088337203 @default.
- W4200295183 cites W2090967904 @default.
- W4200295183 cites W2092100670 @default.
- W4200295183 cites W2096054712 @default.
- W4200295183 cites W2097152121 @default.
- W4200295183 cites W2109006973 @default.
- W4200295183 cites W2109154308 @default.
- W4200295183 cites W2110949039 @default.
- W4200295183 cites W2112792893 @default.
- W4200295183 cites W2113403117 @default.
- W4200295183 cites W2114675905 @default.
- W4200295183 cites W2121627241 @default.
- W4200295183 cites W2123103161 @default.
- W4200295183 cites W2123681603 @default.
- W4200295183 cites W2127966416 @default.
- W4200295183 cites W2132629607 @default.
- W4200295183 cites W2135130294 @default.
- W4200295183 cites W2135180152 @default.
- W4200295183 cites W2144252381 @default.
- W4200295183 cites W2149501736 @default.
- W4200295183 cites W2150981663 @default.
- W4200295183 cites W2151457629 @default.
- W4200295183 cites W2154319440 @default.
- W4200295183 cites W2154936893 @default.
- W4200295183 cites W2155356284 @default.
- W4200295183 cites W2161033884 @default.
- W4200295183 cites W2161211166 @default.
- W4200295183 cites W2161227647 @default.
- W4200295183 cites W2161303529 @default.
- W4200295183 cites W2165740393 @default.
- W4200295183 cites W2168394682 @default.
- W4200295183 cites W2192585006 @default.
- W4200295183 cites W2211953232 @default.
- W4200295183 cites W2294713583 @default.
- W4200295183 cites W2345535076 @default.
- W4200295183 cites W2423210081 @default.
- W4200295183 cites W2486597359 @default.
- W4200295183 cites W2513986326 @default.
- W4200295183 cites W2519597790 @default.
- W4200295183 cites W2560264526 @default.
- W4200295183 cites W2567498952 @default.
- W4200295183 cites W2734498408 @default.