6rjf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 12: Line 12:
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
-
The atomic structure of echovirus 1 (a member of the enterovirus genus of the picornavirus family) has been determined using cryo-crystallography and refined to 3.55 A resolution. Echovirus 1 crystallizes in space group P22121 with a = 352.45, b = 472.15 and c = 483.20 A. The crystals contain one full virus particle in the asymmetric unit allowing for 60-fold noncrystallographic symmetry averaging. The diffraction pattern shows strong pseudo-B-centering with reflections with h + l = 2n + 1 being systematically weak or absent below about 6 A resolution. The size of the unit cell and presence of pseudo-B-centering placed strong constraints on the allowed packing of the icosahedral particle in the crystal lattice. These constraints greatly facilitated the determination of the orientation and position of the virus by reducing the dimensionality of the search, but interactions between the crystallographic and noncrystallographic symmetries rendered the choice of space group ambiguous until very late in the structure determination. This structure determination provides a striking example of the power of packing analysis in molecular replacement and illustrates how subtle interactions between crystallographic and noncrystallographic symmetries can be resolved.
+
There is limited information about the molecular triggers leading to the uncoating of enteroviruses in physiological conditions. Using real-time spectroscopy and sucrose gradients with radioactively-labeled virus we show at 37 degrees C, formation of a low amount of albumin-triggered, metastable, uncoating intermediate of echovirus 1 without receptor engagement. This conversion was blocked by saturating the albumin with fatty acids. High potassium but low sodium and calcium concentrations, mimicking the endosomal environment, also induced the formation of a metastable uncoating intermediate of echovirus 1. Together, these factors boosted the formation of the uncoating intermediate and infectivity of this intermediate was retained, as judged by end-point titration. Cryo-electron microscopy reconstruction of the virions treated with albumin and high potassium, low sodium and low calcium concentrations resulted in a 3.6 A resolution model revealing a fenestrated capsid showing 4 % expansion and loss of the pocket factor, similarly to altered (A-) particles described for other enteroviruses. The dimer interface between VP2 molecules was opened, the VP1 N-termini disordered and most likely externalised. The RNA was clearly visible, anchored to the capsid. The results presented here suggest that extracellular albumin, partially saturated with fatty acids, likely leads to the formation of the infectious uncoating intermediate prior to the engagement with the cellular receptor. In addition, changes in mono- and divalent cations, likely occurring in endosomes, promote capsid opening and genome release.ImportanceThere is limited information about uncoating of enteroviruses in physiological conditions. Here, we focused on physiologically relevant factors that likely contribute to opening of echovirus 1 and other B-group enteroviruses. By combining biochemical and structural data, we show, that before entering cells, extracellular albumin is capable of priming the virus into a metastable, yet infectious intermediate state. The ionic changes that are suggested to occur in endosomes, can further contribute to uncoating and promote genome release, once the viral particle is endocytosed. Importantly, we provide a detailed high-resolution structure of a virion after treatment with albumin and a preset ion composition, showing pocket factor release, capsid expansion and fenestration, and the clearly visible genome still anchored to the capsid. This study provides valuable information about the physiological factors that contribute to the opening of B-group enteroviruses.
-
Structure determination of echovirus 1.,Filman DJ, Wien MW, Cunningham JA, Bergelson JM, Hogle JM Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 2):1261-72. PMID:10089503<ref>PMID:10089503</ref>
+
Extracellular albumin and endosomal ions prime enterovirus particles for uncoating that can be prevented by fatty acid saturation.,Ruokolainen V, Domanska A, Laajala M, Pelliccia M, Butcher SJ, Marjomaki V J Virol. 2019 Jun 12. pii: JVI.00599-19. doi: 10.1128/JVI.00599-19. PMID:31189702<ref>PMID:31189702</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 07:45, 26 June 2019

Echovirus 1 intact particle

PDB ID 6rjf

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6rjf"
Personal tools