Structural Refinement of the OpcA Adhesin Using Molecular Dynamics.
Citation:
Luan, B., Caffrey, M., Aksimentiev, A., Structural Refinement of the OpcA Adhesin Using Molecular Dynamics., Biophysics Journal, 93, 2007, 3058-3069Download Item:
Abstract:
OpcA from Neisseria meningitidis, the causative agent of meningococcal meningitis and septicemia, is an integral
outer membrane protein that facilitates meningococcal adhesion through binding the proteoglycan receptors of susceptible cells.
Two structures of OpcA have been determined by x-ray diffraction to 2A? resolution, revealing dramatically different conformations in
the extracellular loops?the protein domain implicated in proteoglycan binding. In the first structure, a positively charged crevice
formed by loops 1 and 2 was identified as the site for binding proteoglycans, whereas in the second structure the crevice was not
evident as loops 1 and 2 adopted different conformations. To reconcile these results, molecular-dynamics simulations were carried
out on both structures embedded in a solvated lipid bilayer membrane. Free of crystal contacts and crystallization agents, the loops
were observed to undergo large structural transformations, suggesting that the conformation of the loops in either x-ray structure
is affected by crystallization. Subsequent simulations of both structures in their crystal lattices confirmed this conclusion. Based on
our molecular-dynamics trajectories, we propose a model for OpcA that combines stable structural features of the available x-ray
structures. In this model, all five extracellular loops of OpcA have stable secondary structures. The loops form a funnel that leads to
the base of the b-barrel and that includes Tyr-169 on its exposed surface, which has been implicated in proteoglycan binding.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
Author's Homepage:
http://people.tcd.ie/mcaffreDescription:
PUBLISHEDPMID: 17938421
Author: CAFFREY, MARTIN
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Journal ArticleCollections
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Biophysics Journal93
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Nanoscience & MaterialsMetadata
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