User:Kmon86/TMPRSS2

Structural Insights
As a type II transmembrane protease, TMPRSS2 consists of an intracellular N-terminal domain, a Transmembrane domain, a stem region that extends extracellularly and a C-terminal domain that catalyzes its Serine protease (SP) activity. This serine protease activity is orchestrated by a catalytic triad containing the residues His296, Asp345, and Ser441. This noted catalytic triad is typically responsible for the cleaving of basic amino acid residues (lysine or arginine residues)— consistent with what is observed in the S1/S2 cleavage site found in SARS-CoV-2. A notable domain in the stem region that has been examined through mutational analysis is the low density lipoprotein receptor class A domain (LDLRA). Experimental evidence suggests that this domain likely participates in enzymatic activity of the protein and has been examined alongside another motif in the stem region: the scavenger receptor cysteine-rich domain (SRCR). This domain may be implicated in the binding extracellular molecules and other nearby cells. Interestingly, SRCR could have a role in overall proteolytic activity of the protein, which could lead to implications on the overall virulence of SARS-CoV-2.