Molecular Interactions Between Perlecan LG3 and the SARS-CoV-2 Spike Protein Receptor Binding Domain

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2023 Nov 24

PMID 37996967

Authors

Timothy E Gressett

Md Lokman Hossen

Grant Talkington

Milla Volic

Hugo Perez

Purushottam B Tiwari

Prem Chapagain

Gregory Bix

Affiliations

Soon will be listed here.

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global health crisis with significant clinical morbidity and mortality. While angiotensin-converting enzyme 2 (ACE2) is the primary receptor for viral entry, other cell surface and extracellular matrix proteins may also bind to the viral receptor binding domain (RBD) within the SARS-CoV-2 spike protein. Recent studies have implicated heparan sulfate proteoglycans, specifically perlecan LG3, in facilitating SARS-CoV-2 binding to ACE2. However, the role of perlecan LG3 in SARS-CoV-2 pathophysiology is not well understood. In this study, we investigated the binding interactions between the SARS-CoV-2 spike protein RBD and perlecan LG3 through molecular modeling simulations and surface plasmon resonance (SPR) experiments. Our results indicate stable binding between LG3 and SARS-CoV-2 spike protein RBD, which may potentially enhance RBD-ACE2 interactions. These findings shed light on the role of perlecan LG3 in SARS-CoV-2 infection and provide insight into SARS-CoV-2 pathophysiology and potential therapeutic strategy for COVID-19.

Citing Articles

Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy.

Mongiat M, Pascal G, Poletto E, Williams D, Iozzo R Proteoglycan Res. 2024; 2(3).

PMID: 39184370 PMC: 11340296. DOI: 10.1002/pgr2.22.

Molecular interactions between perlecan LG3 and the SARS-CoV-2 spike protein receptor binding domain.

Gressett T, Hossen M, Talkington G, Volic M, Perez H, Tiwari P Protein Sci. 2023; 33(1):e4843.

PMID: 37996967 PMC: 10731540. DOI: 10.1002/pro.4843.

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