CTD in RNA binding

CTD RNA binding

(Zinzula Baumeister BBRC 2020 PMID: 33039147)

RNA binding affinity to a Heptamer

(Zinzula Baumeister BBRC 2020 PMID: 33039147) ca. 4 uM; Sequence: 5’-Cy5-AUUAAAG; measured by MST in MST buffer 0.05% Tween after min incubation

CTD residues involved in RNA binding

(Zinzula Baumeister BBRC 2020 PMID: 33039147) the putative RNA binding site that mapped to residues 248to280 in the SARS-CoV N CTD [21,33] would be conserved inSARS-CoV-2 N. Similarly, residues identified as the secondary RNAbinding site in the SARS-CoV N CTD [33] correspond to Arg 319,Thr334 and Ala 336 (Fig. 3D).

34734665 /2022 : By NMR, here for the first time (liar) we decrypt that CTD with the affinity even higher than that of NTD. Very unexpectedly, ATP, the universal energy currency for all living cells with high cellular concentrations (2-16 mM), specifically binds CTD with Kd of 1.49 ± 0.28 mM (like RBD! - ATP in LLPS regulation). Strikingly, the ATP-binding residues of NTD/CTD are identical in the SARS-CoV-2 variants

MHV CTD may recognize the PS

(Kuo Masters 2016 Virology PMID: 27105451)

CTD + additionally depends upon a segment of the carboxy-terminal tail (domain N3) of the N protein.

model of PS packaging - see: PS

see: How to study functionally important domains of NP

albeit Corbett says N-term is required: NatCom 2021 PMID: 33479198

check!!!

Overlap LLPS domain - RNA binding domain

LLPS domain: NP protein domains required for LLPS - aa 248-266

RNA binding: 248 to 280

Inhibiting RNA binding of CTD should inhibit LLPS