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Annual Review of Virology

Volume 3, 2016

More than Meets the Eye: Hidden Structures in the Proteome

Abstract

A central dogma of molecular biology is that the sequence of a protein dictates its particular fold and the fold dictates its function. Indeed, the sequence → structure → function hypothesis has been a guiding principle by which scientists approach molecular biology. Every student knows that the genome encodes information for the progression from primary sequence to secondary, tertiary, and ultimately quaternary structure. Yet with a growing number of proteins, a fifth level has been identified: rearrangement of existing structures into distinct forms. Recent observations indicate that replication of Ebola virus depends on this fifth level. We believe other viruses with compact genomes and rapid evolution under selective pressure will be a rich source of examples of polypeptides that rearrange to gain added functions. In this review, we describe mechanisms by which viral, prokaryotic, and eukaryotic polypeptides have adopted alternate structures to control or gain function.

Keyword(s): Ebola virus, matrix, metamorphic protein, moonlighting protein, morpheein, transformer

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2016-09-29
2025-04-22
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More than Meets the Eye: Hidden Structures in the Proteome
Annual Review of Virology 3, 373 (2016); https://doi.org/10.1146/annurev-virology-100114-054923
/content/journals/10.1146/annurev-virology-100114-054923
/content/journals/10.1146/annurev-virology-100114-054923
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    Morphs modeling how the VP40 dimer might transition to the matrix-assembling linear hexamer (this video) and the RNA-binding octameric ring (). In each of these videos, N-terminal domains are blue and C-terminal domains are orange. In this video, construction of the hexamer form the dimer, it is modeled that three VP40 dimers gather at the membrane surface. It is hypothesized that an electrostatic interaction with lipid head groups triggers conformational rearrangement and assembly of the hexamer. Note that in the crystal structure of this hexamer (PDB: 4LDD), the central VP40 is upside down. In , the crystal structure of the octameric ring (PDB: 1H2D; Gomis-Ruth et al. 2003, 11:423–33) reveals a 3-nt RNA bound to each N-terminal domain. RNA is illustrated here as the trigger that begins the conformational rearrangement. However, it is not yet known what the trigger of this rearrangement is. We thank Dr. Zachary Bornholdt for the use of these models and videos, originally published as supplemental figures in Bornholdt et al. 2013, 154:763–74.

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    Morphs modeling how the VP40 dimer might transition to the matrix-assembling linear hexamer () and the RNA-binding octameric ring (this video). In each of these videos, N-terminal domains are blue and C-terminal domains are orange. In , construction of the hexamer form the dimer, it is modeled that three VP40 dimers gather at the membrane surface. It is hypothesized that an electrostatic interaction with lipid head groups triggers conformational rearrangement and assembly of the hexamer. Note that in the crystal structure of this hexamer (PDB: 4LDD), the central VP40 is upside down. In this video, the crystal structure of the octameric ring (PDB: 1H2D; Gomis-Ruth et al. 2003, 11:423–33) reveals a 3-nt RNA bound to each N-terminal domain. RNA is illustrated here as the trigger that begins the conformational rearrangement. However, it is not yet known what the trigger of this rearrangement is. We thank Dr. Zachary Bornholdt for the use of these models and videos, originally published as supplemental figures in Bornholdt et al. 2013, 154:763–74.

file format download

    A modeled morph between the two folds of lymphotactin. Residues 61–70 have been modeled into the final structure to facilitate the final morph and allow the complete α-helix to be included. The beginning structure is the originally disordered Ltn10 monomeric form that functions as a chemokine (PDB: 1J8I). The final structure is one protomer of the biologically active dimer, Ltn40, which functions in chemotaxis (PDB: 1J8I).

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  • Article Type: Review Article

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