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Title 

Intrinsically disordered linkers impart processivity on enzymes by spatial confinement of binding domains

Authors 

B SzaboT HorvathE SchadN MurvaiA TantosL KalmarL B ChemesKyou Hoon HanP Tompa

Publisher 

MDPI AG

Issue Date 

2019

Citation 

International Journal of Molecular Sciences

Keywords 

enzyme e ciencypolymeric substrateprocessive enzymedisordered linkerbinding motifbinding domainspatial searchlocal e ective concentration

Abstract 

(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins. Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely e ective and economical. The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors. Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker. (2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized e ective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner. (3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity. We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size. (4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.

URI 

https://doi.org/10.3390/ijms20092119

ISSN 

1422-0067

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-07-10


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