Dataset Information

Conformational Dynamics of Herpesviral NEC Proteins in Different Oligomerization States.

ABSTRACT: All herpesviruses use a heterodimeric nuclear egress complex (NEC) to transport capsids out of host cell nuclei. Despite their overall similar structure, NECs may differ significantly in sequence between different viruses. Up to now, structural information is limited to isolated NEC heterodimers and to large hexagonal lattices made up of hexagonal ring-like structures ("Hexagons"). The present study aimed to expand the existing structural knowledge with information on the dynamics of NECs from different viruses and in different oligomerization states. For this task, comparative molecular dynamics simulations were performed of the free NEC heterodimers from three different viruses (HCMV (human cytomegalovirus), HSV-1 (herpes simplex virus 1), and PRV (pseudorabies virus)). In addition, higher oligomerization states comprising two or six NEC heterodimers were characterized for HCMV and HSV-1. The study revealed that the isolated NEC heterodimers from ?- (HSV-1, PRV) and ?-herpesviruses (HCMV) differ significantly in their dynamics, which can be attributed to a poorly conserved interface region between the NEC subdomains. These differences become smaller for higher oligomerization states, and both HCMV and HSV-1 individual Hexagons exhibit a common region of enhanced dynamics, which might be of functional relevance for the formation of curved vesicle structures or the recognition of hexameric capsid proteins.

SUBMITTER: Diewald B

PROVIDER: S-EPMC6213152 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Conformational Dynamics of Herpesviral NEC Proteins in Different Oligomerization States.

Diewald Benedikt B Socher Eileen E Söldner Christian A CA Sticht Heinrich H

International journal of molecular sciences 20180925 10

All herpesviruses use a heterodimeric nuclear egress complex (NEC) to transport capsids out of host cell nuclei. Despite their overall similar structure, NECs may differ significantly in sequence between different viruses. Up to now, structural information is limited to isolated NEC heterodimers and to large hexagonal lattices made up of hexagonal ring-like structures ("Hexagons"). The present study aimed to expand the existing structural knowledge with information on the dynamics of NECs from d ...[more]

PMID: 30257461

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Project description:All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein's experimentally established conformational substates. Conformational transition of calmodulin from the Ca(2+)-bound to the Ca(2+)-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in proteins.

Dataset Information

Conformational Dynamics of Herpesviral NEC Proteins in Different Oligomerization States.

Publications

Conformational Dynamics of Herpesviral NEC Proteins in Different Oligomerization States.

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