Jelly roll fold

Thejelly rollorSwiss roll foldis aprotein foldorsupersecondary structurecomposed of eightbeta strandsarranged in two four-stranded sheets. The name of the structure was introduced byJane S. Richardsonin 1981, reflecting its resemblance to the jelly orSwiss rollcake.The fold is an elaboration on theGreek key motifand is sometimes considered a form ofbeta barrel. It is very common inviral proteins, particularlyviral capsidproteins.Taken together, the jelly roll and Greek key structures comprise around 30% of theall-beta proteinsannotated in theStructural Classification of Proteins(SCOP) database.
The basic jelly roll structure consists of eightbeta strandsarranged in two four-strandedantiparallelbeta sheets which pack together across ahydrophobicinterface [Where citation... uniprot]. The strands are traditionally labeled B through I for the historical reason that the first solved structure, of a jelly roll capsid protein from thetomato bushy stunt virus, had an additional strand A outside the fold's common core.The sheets are composed of strands BIDG and CHEF, folded such that strand B packs opposite strand C, I opposite H, etc.
A large number ofvirusesbuild their exteriorcapsidsfrom proteins containing either a single or a double jelly roll fold. This shared capsid architecture is thought to reflect ancient evolutionary relationships, possibly dating to before thelast universal common ancestor(LUCA) of cellular life.Other viral lineages use evolutionarily unrelated proteins to build their enclosed capsids, which likely evolved independently at least twiceand possibly many times, with links to proteins of cellular origin.
Single jelly roll capsid (JRC) proteins are found in at least sixteen distinct viralfamilies, mostly withicosahedralcapsid structures and including bothRNA virusesandDNA viruses.Many viruses with single jelly roll capsids arepositive-sense single-stranded RNA viruses. Two groups ofdouble-stranded DNA viruseswith single-JRC capsids are thePapillomaviridaeandPolyomaviridae, both of which have fairly small capsids; in these viruses, the architecture of the assembled capsid orients the axis of the jelly roll parallel or "horizontally" relative to the capsid surface.A large-scale analysis of viral capsid components suggested that the single horizontal jelly roll is the most common fold among capsid proteins, accounting for about 28% of known examples.
Another group of viruses uses single jelly roll proteins in their capsids, but in the vertical rather than horizontal orientation. These viruses are evolutionarily related to the large group of double jelly-roll viruses known as thePRD1-adenovirusviral lineage, with similar capsid architecture realized through assembly of two distinct single jelly-roll major capsid proteins expressed from distinct genes.These single vertical jelly-roll viruses comprise the taxonHelvetiavirae.Known viruses with vertical single jelly roll capsids infectextremophilicprokaryotes.
Double jelly roll capsid proteins consist of two single jelly roll folds connected by a short linker region. They are found in bothdouble-stranded DNA virusesandsingle-stranded DNA virusesof at least ten different viral families, including viruses that infect alldomains of life, and spanning a large capsid size range.In the double jelly roll capsid architecture, the jelly roll axis is oriented perpendicular or "vertically" relative to the capsid surface.
Double jelly roll proteins are believed to have evolved from single jelly roll proteins bygene duplication.It is likely that vertical single jelly roll viruses represent a transitional form, and that the vertical and horizontal jelly roll capsid proteins have independent evolutionary origins from ancestral cellular proteins.The degree of structural similarity among double-jelly-roll virus capsids has led to the conclusion that these viruses likely have a common evolutionary origin despite their diversity in size and in host range; this has become known as thePRD1-adenoviruslineage (Bamfordvirae).Many members of this group have been identified throughmetagenomicsand in some cases have few to no other viral genes in common.Although most members of this group haveicosahedralcapsid geometry, a few families such as thePoxviridaeandAscoviridaehave oval or brick-shaped mature virions; poxviruses such asVacciniaundergo dramatic conformational changes mediated by highly derived double jelly roll proteins during maturation and likely derive from an icosahedral ancestor.Shared double-jelly-roll capsid proteins, along with other homologous proteins, have also been cited in support of the proposedorderMegaviralescontaining thenucleocytoplasmic large DNA viruses(NCLDV).
Initially, it was believed that double jelly roll proteins are unique to viruses, because they were not observed in cellular proteins.However, in 2022, comparison of protein structures revealed several families of bona fide cellular proteins with the double jelly roll fold
Single jelly rolls also occur in non-capsid viral proteins, including minor components of the assembledvirionas well as non-virion proteins such aspolyhedrin.In plant viruses, the 30K superfamilymovement proteinsresponsible for intercellular transport of viral genomes or entire capsids throughplasmodesmatachannels have the single jelly-roll fold and have evolved from the capsid proteins of small icosahedral viruses.
Both single and double jelly roll folds are found in proteins of cellular origin.One class of cellular proteins with single jelly roll fold is thenucleoplasmins, which serve asmolecular chaperoneproteins forhistoneassembly intonucleosomes. TheN-terminaldomainof nucleoplasmins possesses a single jelly roll fold and assembled into a pentamer.Similar structures have since been reported in additional groups ofchromatinremodeling proteins.Jelly roll motifs with identical beta-sheet connectivity are also found intumor necrosis factorligandsand proteins from the bacteriumYersinia pseudotuberculosisthat belong to a class of viral and bacterial proteins known assuperantigens.
More broadly, the members of the extremely diversecupin superfamilyare also often described as jelly rolls; though the common core of the cupin domain structure contains only six beta strands, many cupins have eight.Examples include the non-hemedioxygenaseenzymes(includingalpha-ketoglutarate-dependent hydroxylases) andJmjC-familyhistone demethylases.
Cellular proteins with the double jelly roll fold include glycoside hydrolases of the DUF2961 family,peptide:N-glycosidase F(PNGases F) andpeptidylglycine alpha-amidating monooxygenase.
A notable difference between PNGases F and the other double jelly roll proteins is the absence of the α-helices, which follow the F and F' strands in capsid proteins and DUF2961. The equivalent regions are variable in the PNGases F and contain either long loops or insertions. By contrast, jelly-roll domains of DUF2961 proteins contain an insertion of short β-hairpins upstream of the G and G' strands of the double jelly roll fold. Importantly, DUF2961 family proteins form trimers resembling viral capsomers.
Comparative studies of proteins classified as jelly roll andGreek keystructures suggest that the Greek key proteins evolved significantly earlier than their more topologically complex jelly roll counterparts.Structural bioinformaticsstudies comparing virus capsid jelly-roll proteins to other proteins of known structure indicates that the capsid proteins form a well-separated cluster, suggesting that they are subject to a distinctive set of evolutionary constraints.One of the most notable features of viral capsid jelly roll proteins is their ability to form oligomers in a repeated tiling pattern to produce a closed protein shell; the cellular proteins that are most similar in fold and topology are mostly also oligomers.It has been proposed that viral jelly-roll capsid proteins have evolved from cellular jelly-roll proteins, potentially on several independent occasions, at the earliest stages of cellular evolution.
The name "jelly roll" was first used for the structure composed of an elaboration on theGreek key motifbyJane S. Richardsonin 1981 and was intended to reflect the structure's resemblance to a jelly orSwiss rollcake.The structure has been given a variety of descriptive names, including a wedge, beta barrel, and beta roll. The edges of the two sheets do not meet to form regularhydrogen bondingpatterns, and so it is often not considered to be a truebeta barrel,though the term is in common use in describing viral capsid architecture.Cellular proteins containing jelly roll-like structures may be described as acupinfold, aJmjCfold, or a double-stranded beta helix.