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The primary sequence of the receptor for L-arabinose or Ara-binding protein
(ABP) composed of 306 residues is very different from the
D-glucose/D-galactose-binding protein (GGBP) which consists of 309 residues.
Nevertheless, superimpositioning of the well-refined high resolution structures
of ABP in complex with D-galactose and the GGBP in complex with D-glucose shows
very similar structures; 220 of the residues (or about 70%) have a root mean
square deviation of 2.0 A. From the superpositioning, nine pairs of continuous
segments (consisting of 8-51 residues), mainly alpha-helices and beta-strands
that form the core of the two lobes of the bilobate proteins were found to
exhibit strong sequence homology. The equivalenced structures and aligned
sequences show that many of the polar, as well as aromatic residues, in the
sugar-binding sites located in the cleft between the two lobes are highly
conserved. Surprisingly, however, the exact mode of binding of the D-galactose
in ABP is totally different from that of the D-glucose in GGBP. Using the
structurally aligned sequences of the ABP and GGBP as a template, we have
matched the sequence of the ribose-binding protein (RBP) which consists of 271
residues with the ABP/GGBP pair. Although the nine aligned segments of all three
proteins show little sequence identity, they have significant homology. Four
additional segments of RBP were matched only with GGBP, leading to the alignment
of about 90% of the RBP sequence with the GGBP sequence. Many of the conserved
residues in the binding sites of ABP and GGBP matched with similar residues in
RBP. Additional observations indicate that the GGBP/RBP pair is more closely
related than the ABP/RBP or ABP/GGBP pair. All three binding proteins, which may
have diverged from a common ancestor, serve as primary receptors for bacterial
high affinity active transport systems. Moreover, GGBP and RBP, but not ABP,
also act as receptors for chemotaxis. An exposed site located in one domain,
which includes Gly74, for interacting with the trg transmembrane signal
transducer that is involved in triggering chemotaxis has been located in the
structure of GGBP (Vyas, N.K., Vyas, M.N., and Quiocho, F.A. (1988) Science 242,
1290-1295). Whereas the site is absent in the structure of ABP, it is strongly
predicted to be present in RBP which shares the same trg transducer with GGBP.
The knowledge-based alignment of RBP further revealed two possible additional
peripheral chemotactic sites that show high structural and sequence similarity
between GGBP and RBP only. At least one of these sites, together with the one
proven to exist in the other domain, could be used by the signal transducer with
which both binding proteins interact in a way which the substrate-loaded "closed
cleft" structure could be discriminated from the unliganded "open cleft" form by
the transducer.
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