PROSITE documentation PDOC51744

Helper-component proteinase (HC-Pro) cysteine protease (CPD) domain profile

Potyviruses form one of the most numerous groups of plant viruses and are a major cause of crop loss worldwide. The helper-component proteinase (HC-Pro) is an indispensable, multifunctional protein of members of the genus Potyvirus and other viruses of the family Potyviridae [E1]. It is directly involved in diverse steps of viral infection, such as aphid plant-to-plant transmission, polyprotein processing, and suppression of host antiviral RNA silencing. HC-Pro is generally divided into three functional domains: a N-terminal domain, a central region, and a cysteine protease domain (CPD) in the C-terminal region. The HC-Pro CPD domain has a protease activity that autocatalytically cleaves a Gly-Gly dipeptide at its own C terminus to release HC-Pro from the rest of the viral polyprotein. Cysteine and histidine residues form the catalytic dyad at the active site. The HC-Pro CPD domain constitutes the peptidase family C6 of the CA clan [1,E2].

The structure of the HC-Pro CPD domain adopts a compact oval-shaped α/β fold. The secondary structure elements include four α-helices (α1-α4) and two short β-strands (β1 and β2) arranged in the order α1-α2-α3-β1-β2-α4. In addition, two 3(10) helices are located between α3 and β1 and downstream of α4. The four helices form a helix bundle packed against one face of a short β-hairpin formed by strands β1 and β2 (see <PDB:3RNV>). The catalytic residue Cys is located at the N terminus of helix α1, and the other catalytic residue His is located on strand β2. The substrate binding cleft is lined by the loop connecting helices α2 and α3 and the N-terminal region of helix α1 on one side and by strand β2 on the other side [1].

The profile we developed covers the entire HC-Pro CPD domain.