Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1828, Issue 2, Pages 715-723Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2012.09.002
Keywords
Autotransporter; Membrane protein; Molecular dynamics
Categories
Funding
- BBSRC [BB/H000658/1]
- EPSRC
- CCPBioSim
- University of Southampton
- BBSRC [BB/H000267/1, BB/H000658/1, BB/I019855/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H000658/1, BEP17032, BB/H000267/1, BB/I019855/1, B19456, BBS/B/16011] Funding Source: researchfish
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Hia is a trimeric autotransporter found in the outer membrane of Haemphilus influenzae. The X-ray structure of Hia translocator domain revealed each monomer to consist of an alpha-helix connected via a loop to a 4-stranded beta-sheet, thus the topology of the trimeric translocator domain is a 12-stranded beta-barrel containing 3 alpha-helices that protrude from the mouth of the beta-barrel into the extracellular medium. Molecular dynamics simulations of the Hia monomer and trimer have been employed to explore the interactions between the helices, beta-barrel and connecting loops that may contribute to the stability of the trimer. In simulations of the Hia monomer we show that the central alpha-helix may stabilise the fold of the 4-stranded beta-sheet. In simulations of the Hia trimer, a H-bond network involving residues in the beta-barrel, alpha-helices and loops has been identified as providing stability for the trimeric arrangement of the monomers. Glutamine residues located in the loops connecting the alpha-helices to the beta-barrel are orientated in a triangular arrangement such that each forms 2 hydrogen bonds to each of the corresponding glutamines in the other loops. In the absence of the loops, the beta-barrel becomes distorted. Simulations show that while the trimeric translocator domain beta-barrel is inherently flexible, it is unlikely to accommodate the passenger domain in a folded conformation. Simulations of Hia in an asymmetric model of the outer membrane have revealed membrane-protein interactions that anchor the protein within its native membrane environment. (C) 2012 Elsevier B.V. All rights reserved.
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