TCB Publications - Abstract
B. Luan, M. Caffrey, and A. Aksimentiev. The effect of calcium on the conformation of cobalamin transporter BtuB. PROTEINS: Structure, Function, and Bioinformatics, 78:1153-1162, 2010.
-barrel membrane protein that facilitates transport of cobalamin (vitamin
B12) from the extracellular medium across the outer membrane of Escherichia coli. It is
thought that binding of B12 to BtuB alters the conformation of its periplasm-exposed N-
terminal residues (the TonB box), which enables subsequent binding of a TonB protein and
leads to eventual uptake of B12 into the cytoplasm. Structural studies determined the
location of the B12 binding site at the top of the BtuB’s -barrel, surrounded by
extracellular loops. However, the structure of the loops was found to depend on the
method used to obtain the protein crystals, which—among other factors—differed in
calcium concentration. Experimentally, calcium concentration was found to modulate the
binding of the B12 substrate to BtuB. In this study, we investigate the effect of calcium ions
on the conformation of the extracellular loops of BtuB and their possible role in B12
binding. Using all-atom molecular dynamics, we simulate conformational fluctuations of
several X-ray structures of BtuB in the presence and absence of calcium ions. These
simulations demonstrate that calcium ions can stabilize the conformation of loops 3–4, 5–
6, and 15–16, and thereby prevent occlusion of the binding site. Furthermore, binding of
calcium ions to extracellular loops of BtuB was found to enhance correlated motions in the
BtuB structure, which is expected to promote signal transduction. Finally, we characterize
conformation dynamics of the TonB box in different X-ray structures and find an
interesting correlation between the stability of the TonB box structure and calcium binding.
