The Role of Hexon Protein as a Molecular Mold in Patterning the Protein IX Organization in Human Adenoviruses

Reddy, Vijay

doi:10.1016/j.jmb.2017.06.025

Cited by 13 publications

(17 citation statements)

References 15 publications

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“…The length of IX-C in HAdV-F41 is compatible with both of these arrangements. A cis arrangement of all IX-C would be reminiscent of IX in some non-HAdVs, in which the conformation of IX-C is also more defined (38,43,44). Whereas our data do not allow tracing of individual chains of IX-C, the clear lack of any IX-C density above the IX-N trimer at the icosahedral threefold rules out such a pure cis arrangement of IX-C. One possible, parsimonious interpretation would be that the central IX trimer adopts a trans arrangement, donating one IX-C chain to each of the three IX trimers at local threefold positions that, in turn, have their IX-Cs in cis (Fig.…”

Section: Discussionmentioning

confidence: 99%

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

et al. 2021

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Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present the first structure of an enteric HAdV—HAdV-F41—determined by cryo–electron microscopy to a resolution of 3.8 Å. The structure reveals extensive alterations to the virion exterior as compared to nonenteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of core protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation of enteric HAdVs to a fundamentally different tissue tropism.

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Section: Discussionmentioning

confidence: 99%

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

et al. 2021

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“…Among the so-called minor capsid proteins, pIX forms the most extended and complex arrangements. In previously reported structures of HAdV-C5 and HAdV-D26, this amounts to a tight mesh of ordered protein density that stretches through the canyons between hexons across the virion surface 9,19,34 (Fig. 2A and protruding structures marked with arrows in Fig 1C).…”

Section: Resultsmentioning

confidence: 73%

“…The length of pIX-C in HAdV-F41 is compatible with both of these arrangements. A cis arrangement of all strands would be reminiscent of pIX in some non-human adenoviruses, in which the conformation of pIX-C is also more defined 34,39,40 . Whereas our data don’t allow tracing of individual strands of pIX-C, the lack of any pIX-C density above the pIX-N trimer at the icosahedral 3-fold rules out such a pure cis arrangement of pIX-C. One possible, parsimonious interpretation would be that the central pIX trimer adopts a trans arrangement, donating one pIX-C strand to each of the three pIX trimers at local 3-fold positions which in turn have their pIX-Cs in cis (Fig.…”

Section: Discussionmentioning

confidence: 99%

The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children

Rafie

Lenman

Fuchs

et al. 2020

Preprint

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AbstractHuman adenovirus (HAdV) types F40 and F41 are a leading cause of diarrhoea in children, a prominent cause of childhood mortality worldwide. Here we present the first structure of an enteric HAdV – HAdV-F41 – determined by cryo-EM to a resolution of 3.8Å. The structure reveals extensive alterations to the virion exterior as compared to respiratory and ocular HAdVs, including a unique arrangement of capsid protein IX. In other HAdVs, this protein forms a rigid, virion-covering mesh. In HAdV-F41 its divergent C-terminal half is instead flexible and directed to the outside of the virion in a unique arrangement. We propose the identity of a previously unknown protein – spatially conserved in all HAdV structures determined to date – to be protein V, which bridges the outer, major capsid proteins to the genome and core proteins. We further describe the assembly-induced conformational changes in the penton base protein, a hub connecting the icosahedral capsid to the short and long fibre proteins. These changes include ordering of the penton base’s N-terminus, two loop regions and an α-helix. Our findings provide the structural basis for adaptation to a fundamentally different tissue tropism of enteric HAdVs.

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“…It has been proposed that protein IX in HAdV has two flexible bends that facilitate its coupling to the hexon contours (Fig. 5b) (Reddy, 2017). The different path followed by IX in our HAdV-F41 model may be determined by differences in the hexon residues interacting with IX near the first bend.…”

mentioning

confidence: 87%

“…5b), and the C-terminal domains of IX form coiled coils with only three parallel α-helices located directly on top of their N-terminal triskelions (four such bundles per facet), as exemplified in the bovine adenovirus BAdV-3 structure (Fig. 5a) (Cheng et al, 2014;Hackenbrack et al, 2016;Reddy, 2017;Schoehn et al, 2008). Of all HAdV-F41 structural proteins, protein IX is the least similar to its HAdV-C5 counterpart (Table S2).…”

Section: External Cementing Network: Protein IXmentioning

confidence: 99%

Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural divergence among human adenoviruses

Pérez-Illana

Martínez

Condezo

et al. 2020

Preprint

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AbstractEnteric adenoviruses are one of the main causes of viral gastroenteritis in the world. To carry out a successful infection, the virions must withstand the harsh conditions found in the gut. This requirement suggests that capsid stability must be different from that of other adenoviruses. We have determined the structure of a human enteric adenovirus, HAdV-F41, at 4.0 Å resolution by single particle averaging cryo-electron microscopy, and compared it with that of other adenoviruses with respiratory (HAdV-C5) and ocular (HAdV-D26) tropisms. While the overall structures of hexon, penton base and internal minor coat proteins IIIa and VIII are conserved, we observe partially ordered elements reinforcing the vertex region, which suggests their role in enhancing the physicochemical capsid stability of HAdV-F41. Unexpectedly, we find an organization of the external minor coat protein IX different from all previously characterized human and non-human mastadenoviruses. Knowledge of the structure of enteric adenoviruses can provide a starting point for the design of vectors suitable for oral delivery or intestinal targeting.

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The Role of Hexon Protein as a Molecular Mold in Patterning the Protein IX Organization in Human Adenoviruses

Cited by 13 publications

References 15 publications

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children

Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural divergence among human adenoviruses

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