Investigating intrinsically disordered proteins in paramyxovirus nucleoproteins and phosphoproteins

In this hot review Johnny Habchi and Sonia Longhi discuss intrinsically disordered proteins in a number of viruses – the Nipah, Hendra and measles viruses of the Paramyxoviridae family.

Difficulty in obtaining high-resolution structural data has so far limited understanding of the amount and role of disorder in the viral proteins, but recent research has uncovered that the nucleo- and phosphoproteins contain disordered regions up to 400 residues long.  Using computational approaches they extend these results to the rabies virus and respiratory syncytial virus, showing that structural disorder is conserved and widespread throughout the two viral families.

Researcher insight:
In the last few years there has been a growing interest towards intrinsically disordered proteins related to the understanding of the numerous and diverse functional roles they play. Our group played a pioneering role in focusing the attention of virologists on the abundance of disorder within proteins of the replicative complex of paramyxoviruses. Following these seminal reports in the early 2000s, many other studies that addressed the disordered nature of various viral proteins have been published in subsequent years, leading to revisiting the classical way structure-function relationships in viral proteins are seen. The main advantage of disorder within viral proteins has been proposed to be related to (i) mutational robustness, (ii) pleiotropy, (iii) genetic compaction and (iv) the lessening of evolutionary constraints on overlapping reading frames. In the coming years we aim at further extending these studies by assessing the disordered state of disordered regions from paramyxoviral proteins in the context of intact nucleocapsids as well as in the context of infected cells so as to achieve a more realistic description of the behavior and functional impact of these regions. At the same time we will focus on the identification of small compounds able to block crucial protein-protein interactions mediated by disordered regions and to the assessment of their mechanism of action both in vitro and in vivo.

-Sonia Longhi

To read their thoughts on the functional advantage of disorder in the viral proteins and the resultant biological effects download the article, it’s currently free to access* for 4 weeks:

Structural disorder within paramyxovirus nucleoproteins and phosphoproteins
Johnny Habchi and Sonia Longhi
DOI: 10.1039/C1MB05204G

This article is part of our forthcoming themed issue on intrinsically disordered proteins – check back soon for more hot articles in this issue!

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