The 6-kilodalton peptide 1 of the family Potyviridae: small in size but powerful in function

Abstract

The Potyviridae family is one of the most economically significant groups of plant RNA viruses, causing severe yield losses in agriculturally important crops. Among the viral proteins encoded by potyviruses, the 6-kilodalton peptide 1 (6K1) has emerged as a critical, albeit poorly understood player in viral pathogenesis. Despite its small size, 6K1 exhibits diverse functions, including facilitating the assembly of viral replication complex (VRC), altering host membrane permeability as a viroporin, and interacting with host factors to promote infection. This review synthesizes current knowledge on 6K1, focusing on its structural characteristics, evolutionary conservation, molecular interactions, and potential as a target for antiviral strategies. We further discuss unresolved questions surrounding its putative ion channel activity, polyprotein processing dynamics, and functional parallels with animal virus viroporins. Understanding 6K1's multifunctionality provides new insights into viral infection mechanisms and opens avenues for novel disease control approaches.

Keywords: 6K1; Potyviridae; antiviral targets; membrane remodeling; viral replication complex; viroporin.

Figure 1

The structure of viroporins. (a) Schematic classification of viroporins. IA and IB viroporins contain one TMH with the C terminus in the cytosol and endoplasmic reticulum (ER) lumen or extracellular, respectively; IIA and IIB viroporins contain two TMHs with both N- and C-termini in the cytosol and ER lumen or extracellular, respectively. Type III viroporins contain three TMHs and are not illustrated due to lack of structure; Influenza virus A M2 (IAV M2; PDB ID: 4QKM); Syndrome coronavirus 2 E peptide (SARS-COV-2 E; PDB ID: 8SUZ); Syndrome coronavirus 1 E peptide (SARS-COV-1 E; PDB ID: 5 × 29);Human respiratory syncytial virus SH (HRSV SH); Hepatitis C virus P7 (HCV P7; PDB ID: 2M6X); (b) Structural comparison of TuMV 6K1 and HCV P7. The helical wheels showing TMH 1 (top panel) and TMH 2 (top panel) of the putative pentamer of TuMV 6K1 and HCV P7 hexamer, generated using HeliQuest (numbers indicate the hydrophobic moment). The cartoon views of the TMH 1 (top panel) and TMH 2 (top panel) of the putative pentamer of TuMV 6K1 and HCV P7 hexamer are also shown.

Figure 2

The illustration of 6K1 function during viral infection. (a) 6K1 localizes to ER and form oligomers. It increases membrane permeability, enabling the uptake of Hygromycin B and Sytox Green and enhances potassium ion flux. (b) 6K1 is recruited to VRCs to facilitate viral infection possibly via interacting with host and viral proteins and its viroporin activity. (c) 6K1 adds in viral symptom development, promotes root elongation and improves drought tolerance.

Figure 3

Phylogeny of potyviral 6K1 and its 7K homolog proteins. The tree was constructed using the Neighbor-Joiningmethod and the numbers on branches indicate the bootstrap supporting values. The transmission manner, host specificity, and taxonomy of each virus were indicated. Full information of the tree can be found in the Supplementary Figure 1.

Figure 4

Multiple sequence alignment of potyviral 6K1 and its 7K homologs. The alignment was produced using the Clustal X software and presented using ESPript. The completely and functional conserved residues are shown in red and yellow background, respectively. The full information of this figure can be found in the Supplementary Figure 2.