Critical Residues Involved in the Coassembly of L1 and L2 Capsid Proteins of Human Papillomavirus 16

Chen, Jie; Wang, Daning; Wang, Zhiping; Wu, Kunbao; Wei, Shuangping; Chi, Xiaosa; Qian, Ciying; Xu, Yujie; Zhou, Lizhi; Li, Yuqian; Zhang, Sibo; Li, Tingting; Kong, Zhibo; Wang, Yingbin; Zheng, Qingbing; Yu, Hai; Zhao, Qinjian; Zhang, Jun; Xia, Ningshao; Li, Shaowei; Gu, Ying

doi:10.1128/jvi.01819-22

Cited by 4 publications

(5 citation statements)

References 72 publications

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“…The copyright holder for this preprint this version posted March 22, 2023. ; https://doi.org/10.1101/2023.03.21.533711 doi: bioRxiv preprint this region of L2 plays a role in various activities, including the interaction with L1 (reviewed in (Chen et al, 2023) (Campos, 2017). In fact, a recent paper reports that replacement of three acidic residues at positions 337, 338, and 340 in HPV16 L2 prevents assembly of L2 into the capsid and blocks infection (Chen et al, 2023). We show here that the 337-346 mutant and the 49HA and 49SR replacement mutant L2 proteins lack these acidic residues but are assembled into infectious PsV (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Our results indicate that there are no strict sequence constraints in the CDR for assembly of L2 into PsV, DNA packaging, or virus entry and trafficking to the nucleus. There are reports that this region of L2 plays a role in various activities, including the interaction with L1 (reviewed in (Chen et al, 2023) (Campos, 2017). In fact, a recent paper reports that replacement of three acidic residues at positions 337, 338, and 340 in HPV16 L2 prevents assembly of L2 into the capsid and blocks infection (Chen et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

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Sequence independent activity of a predicted long disordered segment of the human papillomavirus L2 capsid protein during virus entry

Buckley

Choi

et al. 2023

Preprint

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The papillomavirus L2 capsid protein protrudes through the endosome membrane into the cytoplasm during virus entry to bind cellular factors required for intracellular virus trafficking. Cytoplasmic protrusion of HPV16 L2, virus trafficking, and infectivity are inhibited by large deletions in an ~110 amino acid segment of L2 that is predicted to be disordered. The activity of these mutants can be restored by inserting protein segments with diverse compositions and chemical properties into this region, including scrambled sequences, a tandem array of a short sequence, and the intrinsically disordered region of a cellular protein. The infectivity of mutants with small in-frame insertions and deletions in this segment directly correlates with the size of the segment. These results indicate that the length of the disordered segment, not its sequence or its composition, determines its activity during virus entry. Sequence independent but length dependent activity has important implications for protein function and evolution.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sequence independent activity of a predicted long disordered segment of the human papillomavirus L2 capsid protein during virus entry

Buckley

Choi

et al. 2023

Preprint

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“… 13 ). A recent paper reported that replacement of three acidic residues with alanines at positions 337, 338, and 340 in HPV16 L2 prevents assembly of L2 into PsV and blocks infection ( 41 ). The Δ337-346 mutant and the 49HA and 49SR replacement mutants reported here lack these acidic residues but are assembled into PsV that can enter cells and express a reporter gene.…”

Section: Discussionmentioning

confidence: 99%

“…These differences presumably reflect the particular mutations studied or the details of PsV production or the infectivity assays. For example, Chen et al ( 41 ) conducted infectivity assays in 293FT kidney cells, whereas we used the more physiologically relevant HeLa cervical cancer cells and HaCaT keratinocytes. Notably, the requirement that the CDR be a certain minimal length will confound studies of mutations that truncate the CDR.…”

Section: Discussionmentioning

confidence: 99%

Sequence-independent activity of a predicted long disordered segment of the human papillomavirus type 16 L2 capsid protein during virus entry

Oh,

Buckley,

Choi

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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The activity of proteins is thought to be invariably determined by their amino acid sequence or composition, but we show that a long segment of a viral protein can support infection independent of its sequence or composition. During virus entry, the papillomavirus L2 capsid protein protrudes through the endosome membrane into the cytoplasm to bind cellular factors such as retromer required for intracellular virus trafficking. Here, we show that an ~110 amino acid segment of L2 is predicted to be disordered and that large deletions in this segment abolish infectivity of HPV16 pseudoviruses by inhibiting cytoplasmic protrusion of L2, association with retromer, and proper virus trafficking. The activity of these mutants can be restored by insertion of protein segments with diverse sequences, compositions, and chemical properties, including scrambled amino acid sequences, a tandem array of a short sequence, and the intrinsically disordered region of an unrelated cellular protein. The infectivity of mutants with small in-frame deletions in this segment directly correlates with the size of the segment. These results indicate that the length of the disordered segment, not its sequence or composition, determines its activity during HPV16 pseudovirus infection. We propose that a minimal length of L2 is required for it to protrude far enough into the cytoplasm to bind cytoplasmic trafficking factors, but the sequence of this segment is largely irrelevant. Thus, protein segments can carry out complex biological functions such as Human papillomavirus pseudovirus infection in a sequence-independent manner. This finding has important implications for protein function and evolution.

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“…It is important to note that HPV is a double-stranded DNA and non-enveloped virus, and its capsid contains two proteins, major capsid protein L1 and minor capsid protein L2 [ 14 ]. When HPV adheres to the cell surface, the amino acids 108–126 of the minor capsid protein L2 specifically bind to the subunit S100A10 of A2t on the membrane of host cells, with an association constant (k) of 10 5 M −1 [ 13 ].…”

Section: Human Papillomavirusmentioning

confidence: 99%

Annexin A2: the missing piece in the puzzle of pathogen-induced damage

Liao

et al. 2023

Virulence

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Annexin A2 is a Ca 2+ regulated protein belonging to the Annexin family and is found in the cytoplasm and cell membrane. It can exist in a monomeric form or in a heterotetrameric form with the S100A10 dimer. The research on Annexin A2 in tumours is currently active, and studies on its role in pathogen infection are increasing. Annexin A2 plays a crucial role in the life cycle of viruses by mediating adhesion, internalization, uncoating, transport, and release. In the case of parasites, bacteria, mycoplasma, fungi, and other pathogens, Annexin A2 binds to the ligand on the pathogen, which mediates the pathogen’s adhesion to the host cell, ultimately leading to infection and damage to the host. Furthermore, some studies have developed biological or chemical drugs that target Annexin A2, which have demonstrated promising anti-infective effects. Thus, targeting Annexin A2 may present a promising therapeutic approach for the treatment of diverse infectious diseases. In summary, this paper provides an overview of Annexin A2 and its role in various pathogens. It highlights its regulation of pathogen infection and its potential as a therapeutic target for the treatment of infectious diseases.

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Critical Residues Involved in the Coassembly of L1 and L2 Capsid Proteins of Human Papillomavirus 16

Cited by 4 publications

References 72 publications

Sequence independent activity of a predicted long disordered segment of the human papillomavirus L2 capsid protein during virus entry

Sequence independent activity of a predicted long disordered segment of the human papillomavirus L2 capsid protein during virus entry

Sequence-independent activity of a predicted long disordered segment of the human papillomavirus type 16 L2 capsid protein during virus entry

Annexin A2: the missing piece in the puzzle of pathogen-induced damage

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