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Query: UNIPROT:P06889 (Mol)
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Type IV pilus genes have been shown to be required for social gliding motility in Myxococcus xanthus. We report the discovery of four additional pil genes: pilD, a homologue of type IV prepilin leader peptidases; and pilG, pilH and pilI, which have no known homologues in other type IV pilus systems. pilH encodes an ATP-binding cassette (ABC) transporter homologue, the first such homologue to be required for the biogenesis of any bacterial pilus type. pilG and pilI are co-transcribed with pilH and appear to be functionally related to pilH. Null mutants of pilG, pilH and pilI all lack social motility, are deficient in pilus production, have elevated sporulation efficiencies and display similar developmental abnormalities. In addition, all three mutations reduced the amount of PilA found in the supernatant after cells were sedimented from liquid culture. We suggest that the products of these three genes form a single ABC exporter complex, in which pilI is an integral membrane protein with membrane-spanning domains, and pilG is an accessory factor. The complex may participate in pilus assembly and/or the export of PilA pilin.
Mol Microbiol 1998 Sep
PMID:The pilH gene encodes an ABC transporter homologue required for type IV pilus biogenesis and social gliding motility in Myxococcus xanthus. 976 92

Interactions between domains of ATP-binding cassette (ABC) transporters are of great functional importance and yet are poorly understood. To gain further knowledge of these protein-protein interactions, we studied the inner membrane complex of the maltose transporter of Escherichia coli. We focused on interactions between the nucleotide-binding protein, MalK, and the transmembrane proteins, MalF and MalG. We incubated purified MalK with inverted membrane vesicles containing MalF and MalG. MalK bound specifically to MalF and MalG and reconstituted a functional complex. We used this approach and limited proteolysis with trypsin to show that binding and hydrolysis of ATP, inducing conformational changes in MalK, modulate its interaction with MalF and MalG. MalK in the reconstituted complex was less sensitive to protease added from the cytoplasmic side of the membrane, and one proteolytic cleavage site located in the middle of a putative helical domain of MalK was protected. These results suggest that the putative helical domain of the nucleotide-binding domains is involved, through its conformational changes, in the coupling between the transmembrane domains and ATP binding/hydrolysis at the nucleotide-binding domains.
Mol Microbiol 1998 Oct
PMID:In vitro interaction between components of the inner membrane complex of the maltose ABC transporter of Escherichia coli: modulation by ATP. 979 Nov 80

Transcription of the mal regulon of Escherichia coli K-12 is regulated by the positive activator, MalT. In the presence of ATP and maltotriose, MalT binds to decanucleotide MalT boxes that are found upstream of mal promoters and activates transcription at these sites. The earliest studies of the mal regulon, however, suggested a negative role for the MalK protein, the ATP-binding cassette subunit of the maltose transporter, in regulating mal gene expression. More recently, it was found that overexpression of the MalK protein resulted in very low levels of mal gene transcription. In this report we describe the use of tagged versions of MalT to provide evidence that it physically interacts with the MalK protein both in vitro and in vivo. In addition, we show that a novel malK mutation, malK941, results in an increased ability of MalK to down-modulate MalT activity in vivo. The fact that the MalK941 protein binds but does not hydrolyse ATP suggests that the MalK941 mutant protein mimics the inactive, ATP-bound form of the normal MalK protein. In contrast, cells with high levels of MalK ATPase show a reduced ability to down-modulate MalT and express several mal genes constitutively. These results are consistent with a model in which the inactive form of MalK down-modulates MalT and decreases transcription, whereas the active form of MalK does not. This model suggests that bacteria may be able to couple information about extracellular substrate availability to the transcriptional apparatus via the levels of ATP hydrolysis associated with transport.
Mol Microbiol 1998 Nov
PMID:The ATP-binding cassette subunit of the maltose transporter MalK antagonizes MalT, the activator of the Escherichia coli mal regulon. 982 19

ATP-binding cassette (ABC) systems, also called traffic ATPases, are found in eukaryotes and prokaryotes and almost all participate in the transport of a wide variety of molecules. ABC systems are characterized by a highly conserved ATPase module called here the ABC module, involved in coupling transport to ATP hydrolysis. We have used the sequence of one of the first representatives of bacterial ABC transporters, the MalK protein, to collect 250 closely related sequences from a nonredundant protein sequence database. The sequences collected by this objective method are all known or putative ABC transporters. After having eliminated short protein sequences and duplicates, the 197 remaining sequences were subjected to a phylogenetic analysis based on a mutational similarity matrix. An unrooted tree for these modules was found to display two major branches, one grouping all collected uptake systems and the other all collected export systems. This remarkable disposition strongly suggests that the divergence between these two functionally different types of ABC systems occurred once in the history of these systems and probably before the differentiation of prokaryotes and eukaryotes. We discuss the implications of this finding and we propose a model accounting for the generation and the diversification of ABC systems.
J Mol Evol 1999 Jan
PMID:Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. 987 74

Membrane proteins of the ATP-binding cassette (ABC) superfamily are involved in the transport of diverse substrates across organellar and plasma membranes of the mammalian cell. Most human ABC proteins identified to date are associated with genetically linked diseases or clinically relevant phenotypes. We describe a new human half-molecule ABC protein, designated M-ABC1, that contains a predicted single membrane and ATP-binding cassette domain. M-ABC1 is localized to membranes of the mitochondria and its transcript is expressed in all tissues. The N-terminal region of the M-ABC1 protein was shown to function independently as a mitochondrial signal sequence by its ability to target the green fluorescent protein to the mitochondria. The monomeric 60 kDa M-ABC1 protein was chemically crosslinked in vivo into a major protein species of 120-130 kDa, thereby confirming that M-ABC1 exists within a higher ordered ABC protein complex. A dominant negative repression approach using M-ABC1 protein with site-directed mutations in its Walker A motif revealed that the mutant protein was rapidly degraded and indicated that the intact Walker A motif of M-ABC1 was required for its stability. The identification of M-ABC1 extends the known distribution of members of the ABC protein family into the mammalian mitochondrion.
J Mol Biol 1999 Jan 08
PMID:Identification and characterization of a mammalian mitochondrial ATP-binding cassette membrane protein. 987 13

PFGCN20 is a member of the ATP-binding cassette family of proteins that is closely related to the yeast translational regulator Gcn20p. We have generated a polyclonal antibody against the N-terminal region of PFGCN20 and studied the cellular localization of PFGCN20 throughout the erythrocytic life cycle of Plasmodium falciparum. PFGCN20 was found to be present at all stages and a pronounced export of PFGCN20 into the erythrocyte was observed in the trophozoite and schizont stages. In the indirect immunofluorescence assay, PFGCN20 was found to display significant colocalization with antigens detected by the monoclonal antibody 41E11. In contrast, there was only a minimal overlap of PFGCN20 localization with EMP2 and HRP2. Immunoelectron microscopy demonstrated a pronounced accumulation of PFGCN20 in the lumen of the parasitophorous vacuole and deconvolution fluorescence microscopy showed membrane association with selective regions of a tubovesicular network in the red cell. We also observed a concentration of PFGCN20 in electron-dense plaques just underneath the parasite's plasma membrane and an association of PFGCN20 with cytoplasmic vesicular structures within the parasite. The observed export of PFGCN20 and its association with the tubovesicular network in host red cells, may be indicative of the fact that PFGCN20 functions as ATP-binding subunit of an unknown multimeric ABC-transporter. The cytoplasmic localization of PFGCN20 in the parasite, however, suggests that the involvement of PFGCN20 in translational regulation or other cytoplasmic biological functions cannot be ruled out.
Mol Biochem Parasitol 1998 Nov 30
PMID:The human malaria parasite Plasmodium falciparum exports the ATP-binding cassette protein PFGCN20 to membrane structures in the host red blood cell. 987 89

The wbp cluster of Pseudomonas aeruginosa O5 encodes a number of proteins involved in biosynthesis of the heteropolymeric and Wzy-dependent B-band O antigen, including Wzy, the O-antigen polymerase, and Wzz, the regulator of O-antigen chain length. A gene (formerly wbpF), contiguous with wzy in the wbp cluster, is predicted to encode a highly hydrophobic protein with multiple membrane-spanning domains. This secondary structure is consistent with that of Wzx (RfbX), the putative O-antigen unit translocase or "flippase." Insertion of a Gmr cassette at two separate sites within the putative wzx gene led in both cases to the loss of B-band lipopolysaccharide (LPS) O-antigen production. To our knowledge, this is the first report of the successful generation of chromosomal wzx gene replacement mutations. Surprisingly, inactivation of wzx also led to a marked delay in production of the ATP-binding cassette-transporter-dependent, D-rhamnose homopolymer, A-band LPS. This effect on A-band LPS synthesis was alleviated by supplying multiple copies of WbpL in trans. WbpL, a WecA (Rfe) homologue, was shown recently to be essential for the initiation of both A-band and B-band LPS synthesis in P. aeruginosa O5 (H. L. Rocchetta, L. L. Burrows, J. C. Pacan, and J. S. Lam, Mol. Microbiol. 28:1103-1119, 1998). These results suggest that the delay in A-band LPS production may arise from insufficient access to WbpL when the completed B-band O unit is not successfully translocated to the periplasm. Without adequate WbpL, A-band LPS synthesis is delayed. A subset of wzx mutants appeared to have accumulated second-site mutations which either restored the normal expression of A-band LPS or abolished A-band expression completely. Complementation studies showed that all of the additional mutations affecting LPS synthesis that were characterized in this study were located within the B-band LPS genes.
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PMID:Effect of wzx (rfbX) mutations on A-band and B-band lipopolysaccharide biosynthesis in Pseudomonas aeruginosa O5. 992 63

Periplasmic binding proteins (PBPs) serve as receptors for various water-soluble ligands in ATP-binding cassette (ABC) transport systems, and form one of the largest protein families in eubacterial and archaebacterial genomes. They are considered to be derived from a common ancestor, judging from their similarities of three-dimensional structure, their mechanism of ligand binding and the operon structure of their genes. Nevertheless, there are two types of topological arrangements of the central beta-sheets in their core structures. It follows that there must have been differentiation in the core structure, which we call "domain dislocation", in the course of evolution of the PBP family. To find a clue as to when the domain dislocation occurred, we constructed phylogenetic trees for PBPs based on their amino acid sequences and three-dimensional structures, respectively. The trees show that the proteins of each type clearly cluster together, strongly indicating that the change in the core structure occurred only once in the evolution of PBPs. We also constructed a phylogenetic tree for the ABC proteins that are encoded by the same operon of their partner PBP, and obtained the same result. Based on the phylogenetic relationship and comparison of the topological arrangements of PBPs, we obtained a reasonable genealogical chart of structural changes in the PBP family. The present analysis shows that the unidirectional change of protein evolution is clearly deduced at the level of protein three-dimensional structure rather than the level of amino acid sequence.
J Mol Biol 1999 Feb 12
PMID:Domain dislocation: a change of core structure in periplasmic binding proteins in their evolutionary history. 993 Dec 66

The genes ftsE and ftsX are organized in one operon together with ftsY. FtsY codes for the receptor of the signal recognition particle (SRP) that functions in targeting a subset of inner membrane proteins. We have found no indications for a structural relationship between FtsE/X and FtsY. Evidence is presented that FtsE and FtsX form a complex in the inner membrane that bears the characteristics of an ATP-binding cassette (ABC)-type transporter. FtsE is a hydrophilic nucleotide-binding protein that has a tendency to dimerize and associates with the inner membrane through an interaction with the integral membrane protein FtsX. An FtsE null mutant showed filamentous growth and appeared viable on high salt medium only, indicating a role for FtsE in cell division and/or salt transport.
Mol Microbiol 1999 Feb
PMID:Molecular characterization of Escherichia coli FtsE and FtsX. 1004 40

The inwardly-rectifying K+ channel Kir6.2 serves as a common pore-forming core in various ATP-sensitive K+ (KATP) channels, and it is through assembly with sulfonylurea-receptor (SUR) isoforms, which are ATP-binding cassette (ABC) proteins, that tissue-specific channel phenotypes can be generated. In this regard, Kir6.2 has been shown to physically associate with SUR1 to form the pancreatic KATP channel. While cardiac KATP channel activity can be reconstituted by coexpression of Kir6.2 with a distinct SUR isoform, SUR2A, no direct proof has been provided for physical association between these two proteins. Therefore, we tested, by a coimmunoprecipitation procedure in conjunction with an amino-terminal Kir6.2-antibody, physical association between recombinant Kir6.2 and SUR2A. From a mixture of Kir6.2 and SUR2A in vitro-translated proteins, the Kir6.2-specific antibody coimmunoprecipitated 38-kDa and 140-kDa proteins corresponding to Kir6.2 and SUR2A, respectively. In the absence of Kir6.2, SUR2A was not precipitated by the anti-Kir6.2 antibody, indicating that the antibody recognized SUR2A only when SUR2A formed a complex with Kir6.2. A Kir6.2 deletion mutant lacking 37 amino acids from the carboxyterminus still coimmunoprecipitated with SUR2A, indicating that the distal carboxy-terminus of Kir6.2 is unnecessary for subunit association. Kir6.2 mutants lacking more proximal carboxy-terminus regions, including the M2 transmembrane domain, failed to immunoprecipitate SUR2A, suggesting that the proximal carboxyterminus together with the M2 domain are required for channel assembly. These deletion constructs supported cellular distribution of Kir6.2. Thus, the present study provides direct evidence for physical association between Kir6.2 and SUR2A, essentially reconstituting the cardiac KATP channel in vitro. The demonstration of complex formation between Kir6.2 and SUR2A indicates that the structural basis for channel function may rely on direct physical interaction of the two subunits.
J Mol Cell Cardiol 1999 Feb
PMID:Physical association between recombinant cardiac ATP-sensitive K+ channel subunits Kir6.2 and SUR2A. 1009 54


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