Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Identification of conserved mortise-tenon joints in outer membrane proteins and their influence on β-barrel stability (#198)

Natalie Quarmby 1 , Matthew D Johnson 2 , Megan L O'Mara 3 , Denisse L Leyton 1 2
  1. Medical School, Australian National University, Acton, ACT, Australia
  2. Research School of Biology, Australian National University, Acton, ACT, Australia
  3. Research School of Chemistry, Australian National University, Acton, ACT, Australia

Outer membrane β-barrel proteins (OMPs) form cylindrical structures that function as pores, substrate specific transporters, and membrane plugs. The structural stability of a β-barrel protein is largely dependent on the interactions between neighbouring antiparallel β-strands. Previously, we characterised one such interaction, the mortise-tenon joint. Formed from the interaction between a luminal aromatic residue on one β-strand and a glycine on the adjacent β-strand, mortise-tenon joints were shown to contribute to the folding and stability of the Pet autotransporter β-barrel. Here we survey the prevalence of these mortise-tenon joints in all OMP structures. The unique 60,90 chiral 1 and 2 angles, which are a definitive feature of the tenon side chains, were used to screen the Protein Data Bank for tryptophan, tyrosine and phenylalanine tenon joints. Mortise-tenon joints were then confirmed using structural analyses. The frequency of mortise-tenon joints was correlated with the biological function, size, and number of β-strands of each structure. Our results indicate that mortise-tenon joints are highly conserved within OMP families and that the number of mortise-tenon joints vary between different OMP families. In addition, we found that β-barrels involved in the transportation of proteinaceous substrates have a high frequency of mortise-tenon joints. In contrast, we observed that mortise-tenon joints are under-represented in small β-barrels, which form plug structures, and in β-barrels that employ other mechanisms of stabilisation, such as oligomerisation. Our results are discussed in relation to the structural requirements of OMPs and the possible role of mortise-tenon joints in β-barrel stability. Understanding of inter β-sheet interactions and their role in β-barrel stability is also important to the rational design of synthetic β-barrels.