Multiscale modelization in an icosahedral non-enveloped virus: capsid pH sensing and disassembly induced by alkaline pH
CIC nanoGUNE Seminars
- Speaker
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Diego M. Guerin, Instituto Biofisika, UPV
- When
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2018/01/22
12:00 - Place
- nanoGUNE seminar room, Tolosa Hiribidea 76, Donostia - San Sebastian
- Add to calendar
-
iCal
Triatoma virus (TrV; Dicistroviridae:Triatovirus) is virus very structurally
similar to many animal viruses like poliovirus and rhinovirus. These viruses
are composed of a spherical capsid that encloses the genome (a single chain of
RNA). This type of capsid is built of about 240 proteins displaying
icosahedral symmetry, and has a diameter of about 30nm. Experimental results
obtaining with TrV show that the capsid of this virus is stable at acidic
conditions but disassembles and releases the genome under alkaline
environments (i.e. external pH>8)1,2. In this work we show the modelling of
three connected processes involved in the capsid destabilization that allow
the genome to be released. 1) Using Molecular Dynamic simulations we describe
the process by which a structural cation allows the hydration of the
hydrophobic cavity along the icosahedral five-fold axis. Whitin the narrowest
par of the cavity this hydration forms a water wire, a structure already
observed in carbon nanotubes and in cavities of several hydrophobic proteins
(membrane proteins). 2) Starting from the hydrated cavity as obtained before,
we simulate an ion channel transport using Quantum theoretical Methods (QM).
Our analysis shows that protons can escape from the capsid interior along the
water wire following a step-by step jumping pathway (called Grotthuss-like
mechanism3), and 3) Assuming that the proton's leak produces an internal
charge imbalance, by employing a Coarse-grain approximation we model how
internal electrostatic forces can destabilize and crack the capsid to allow
the genome release. These results are in line with current experimental data
on TrV, and could describe the events that drive the disassembly of alkaline
pH-labile icosahedral viral capsids. Moreover, our modelizations give base to
postulate the existence of proton-diodes in viral capsids, which function
would be to sense the environmental pH (Viso el al. 2018 4).
**Key words:** Capsid disassembly; hydrophobic gate; Grotthus-like mechanism;
Coarse-grain; Triatoma virus
**References:** 1\. Agirre J, et al. (2013) J Gen Virol. 94(Pt 5):1058-1068;
2. Snijder J, et al. (2013) Nat Chem 5:502–509; 3. Riccardi D, et al.,
(2006) JACS 128:16302-16311; 4. Viso, J., et al., 2018. Under revision; 5.
Sánchez-Eugenia et al., 2016. J. Gen. Virol. 97:2769-2779
**Host** : A.M. Bittner