SARS-CoV-2 Papain-Like protease (PLpro)

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1. INSERT GENERAL STRUCTURE ON THE RIGHT
2. INSERT TABLE: name (nsp3), protein full name (Papain-like protease) length (1945), range (819-2763), role (responsible for release of NSP1, NSP2 and NSP3 from the N-terminal region of pp1a and 1ab), size (200kDa) Acession No. (YP_009725299)

Contents 1 Structural highlights 2 Function 3 Recognition motif 4 Similarity - SARS-CoV PLpro and MERS-CoV 5 References

Structural highlights

Papain-like protease is a domain from the membrane anchored multi-domain protein nsp3.

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The substructure components of PLpro include a catalytic domain and Ubl domain

SARS-CoV-2 PLpro is subdivided into four subdomains, the N-terminal ubiquitin-like domains (Ubl, beta1-3), the alpha-helical Thumb domain (alpha2-7), the beta-stranded Finer Domain (beta4-7) and the Palm domain (beta8-13)

Function

Is an enzyme that have a catalytic activity and play a role in the interactions with ubiquitin

The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) plays essential roles in virus replication and immune evasion.

PLpro and Mpro (main protease) are together responsible for the processing of viral polyproteins (pp1a and pp1ab) coded by ORF1ab and ORF1a yielding mature viral proteins. Releae of NSP1, NSP2 and NSP3 from the N-terminal region of polyproteins pp1a and pp1ab

In addiction, PLpro suppresses innate immunity through reversing the ubiquitination and ISGylation events.

PLpro functions through its cysteine protease activity. The catalytic triad is composed of C111, which acts as a nucleophile, H273, which functions as a general acid-base, and D293, which helps in the deprotonation of cysteine residue. That active site residues are located at the interface between the thumb and palm subdomains.

The CoV PLpro is associated with a lowered immune responde through its deubiquitinating activity.

Recognition motif

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LKGG Recognized by the substrate binding mechanism. The conformational change of the BL2 loop located between beta11-12 strands (residues 267-271). This flexible loop that recognizes P2-P4 pf the LXGG motif on substrate

Similarity - SARS-CoV PLpro and MERS-CoV

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SARS-CoV-2 and SARS-CoV 82.59% SARS-CoV-2 and MERS-CoV 30.06%

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References