RESUMO
Haemophilus influenzae HxuA is a cell-surface protein with haem-haemopexin binding activity which is key to haem acquisition from haemopexin and thus is one of the potential sources of haem for this microorganism. HxuA is secreted by its specific transporter HxuB. HxuA/HxuB belongs to the so-called two-partner secretion systems (TPSs) that are characterized by a conserved N-terminal domain in the secreted protein which is essential for secretion. Here, the 1.5â Å resolution structure of the secretion domain of HxuA, HxuA301, is reported. The structure reveals that HxuA301 folds into a ß-helix domain with two extra-helical motifs, a four-stranded ß-sheet and an N-terminal cap. Comparisons with other structures of TpsA secretion domains are reported. They reveal that despite limited sequence identity, strong structural similarities are found between the ß-helix motifs, consistent with the idea that the TPS domain plays a role not only in the interaction with the specific TpsB partners but also as the scaffold initiating progressive folding of the TpsA proteins at the bacterial surface.
Assuntos
Proteínas da Membrana Bacteriana Externa/química , Proteínas de Transporte/química , Haemophilus influenzae/química , Heme/química , Hemopexina/química , Modelos Moleculares , Sequência de Aminoácidos , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Sistemas de Secreção Bacterianos/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Haemophilus influenzae/metabolismo , Heme/metabolismo , Hemopexina/metabolismo , Dados de Sequência Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia Estrutural de ProteínaRESUMO
The two-partner secretion (TPS) pathway is a branch of type V secretion. TPS systems are dedicated to the secretion across the outer membrane of long proteins that form extended ß-helices. They are composed of a 'TpsA' cargo protein and a 'TpsB' transporter, which belongs to the Omp85 superfamily. This basic design can be supplemented by additional components in some TPS systems. X-ray structures are available for the conserved TPS domain of several TpsA proteins and for one TpsB transporter. However, the molecular mechanisms of two-partner secretion remain to be deciphered, and in particular, the specific role(s) of the TPS domain and the conformational dynamics of the TpsB transporter. Deciphering the TPS pathway may reveal functional features of other transporters of the Omp85 superfamily.