2.3 Predicting the impact of amino acid substitutions on the
function of TMPRSS2
The human TMPRSS2 protein sequence was selected as the reference to
screen all amino changes across 164 species. The impact of an amino acid
change on the structure and function of the TMPRSS2 was finally
estimated by the PolyPhen-2[18].
Scores were calculated by PolyPhen-2 for estimating the effects of amino
acid changes on the protein, and were divided into three groups:
probably damaging (score ≥ 0.957), possibly damaging
(0.453 < score < 0.956) and benign (score ≤ 0.452).
To facilitate the prediction of capability of TMPRSS2 for S-protein
priming, we marked each species based on the PolyPhen-2 scores. We only
focused on domain regions. Firstly, we considered the full mark as 100,
as the human TMPRSS2 protein sequence has been proved to work in human
cells. Secondly, if amino acid changes was not found to occur at
catalytic triad; 0.1, 0.5 and 1 point deduction was made for “benign”,
“possibly damaging” and “probably damaging”, respectively. Thirdly,
if one amino acid change occurred at the catalytic triad of TMPRSS2
(His296, Ser441 and Asp435), 15 points deduction was made for three
reasons: 1) the change of catalytic triad greatly reduced the enzyme
activity; 2) the poultry were proven much less susceptible to
SARS-CoV-2; 3) scores of all Aves were less than 85. Finally, we ranked
scores for all species to predict the potential function of TMPRSS2 for
S-protein priming of SARS-CoV-2.
3 Results