2.A.56.1.6
The Na⁺-dependent sialic acid uptake porter, SiaPQM. SiaQ and SiaM form a 1:1 stoichiometric complex (Mulligan et al., 2012).  The structure of a Vibrio ortholog has been determined by cryoEM (Peter et al. 2022). The protein complex is composed of 16 TMSs in SiaQ (4 TMSs) and SiaM (12 TMSs) that are structurally related to multimeric elevator-type transporters. The idiosyncratic Q-domain of TRAP transporters enables the formation of a monomeric elevator architecture.  A model of the tripartite PQM complex is experimentally validated and reveals the coupling of the substrate-binding P protein to the transporter domains. Peter et al. 2022 studied the formation of the tripartite complex and investigated the impact of interface mutants. The 3-D structure of the he cryo-EM structure of the sialic acid TRAP transporter SiaQM from Photobacterium profundum at 2.97 Å resolution. SiaM comprises a "transport" domain and a "scaffold" domain, with the transport domain consisting of helical hairpins as seen in the sodium ion-coupled elevator transporter VcINDY. The SiaQ protein forms intimate contacts with SiaM to extend the size of the scaffold domain, suggesting that TRAP transporters may operate as monomers, rather than the typically observed oligomers for elevator-type transporters. Davies et al. 2023 identified the Na⁺ and sialic acid binding sites in SiaM from Photobacterium profundum at 2.97 Å resolution and demonstrated a strict dependence on the substrate-binding protein SiaP for uptake. They reported the SiaP crystal structure that, together with docking studies, suggested the molecular basis for how sialic acid is delivered to the SiaQM transporter complex. They proposed a model for substrate transport by TRAP proteins as an 'elevator-with-an-operator' mechanism (Davies et al. 2023).  A hydrophobic surface pocket of the SBP is crucial for the allosteric mechanism and for the conformational rearrangement that occurs upon binding of sialic acid to the SBP (Schneberger et al. 2024).