Structural model of ATP-binding proteing associated with cystic fibrosis, multidrug resistance and bacterial transport

Abstract

The ATP-binding cassette (ABC) superfamily of transport systems now includes over thirty proteins that share extensive sequence similarity and domain organization. This superfamily includes the well characterized periplasmic binding protein-dependent uptake systems of prokaryotes, bacterial exporters, and eukaryotic proteins including the P-glycoprotein associated with multidrug resistance in tumours (MDR), the STE6 gene product that mediates export of yeast a-factor mating pheromone, pfMDR that is implicated in chloroquine resistance of the malarial parasite, and the product of the cystic fibrosis gene (CFTR). Here we present a tertiary structure model of the ATP-binding cassettes characteristic of this class of transport system, based on similarities between the predicted secondary structures of members of this family and the previously determined structure of adenylate kinase. This model has implications for both the molecular basis of transport and cystic fibrosis and provides a framework for further experimentation.

Energy transduction in lactic acid bacteria

“…The system includes a sugar-binding lipoprotein (MsmE), two membrane proteins (MsmF, MsmG) and a protein (MsmK) containing a highly conserved ATP-binding cassette. The recognition of the ATP-binding cassette is often used to designate the transport systems as membcrs of the ABC transport superfamily [22,23]). The genes encoding the Msm proteins are clustered together with genes encoding a e~-galactosidase (Aga), sucrose phosphowlasc (GtfA), dextran glucosidase (DexB).…”

“…Thc oligopcptide transporl system is composed of five proteins, encoded by the oppFDCBA operon. OppD and OppF are homologous to the ATP binding protein(s) (domains) of the ABC-transporter superfamily [22,23], and most likely l\)rm the target for tile (completc) inhibition of oligopeptide transport by ortho-vanadate [72]. OppB and OppC are highly hydrophobic proteins, that on basis of hydropathy analyses, are able to span the cytoplasmic membrane in ~f-helical configuration six times.…”

Mutational analysis of the Saccharomyces cerevisiae ATP‐binding cassette transporter protein Ycf1p

“…These proteins consist of two domains: a highly hydrophobic region with multiple ␣-helical membrane-spanning segments and a characteristic nucleotide-binding domain (NBD) (Higgins, 1992). The high degree of sequence conservation in the NBDs of ABC transporters serves to separate these proteins into a distinct family, set apart from the large number of nucleotide-binding proteins (Hyde et al, 1990).…”

Assembly and Misassembly of Cystic Fibrosis Transmembrane Conductance Regulator: Folding Defects Caused by Deletion of F508 Occur Before and After the Calnexin-dependent Association of Membrane Spanning Domain (MSD) 1 and MSD2

“…Individuals who inherit two mutant forms of CFTR have exceedingly viscous mucous and, due to chronic lung infections, develop cystic fibrosis and often die from lung failure. CFTR is a member of the ATP-binding cassette (ABC) transporter superfamily (Hyde et al, 1990) and is a 1480-amino acid protein that contains two membrane spanning domains (MSDs), MSD1 and MSD2; two cytosolic nucleotide binding domains (NBDs), NBD1 and NBD2; and a regulatory (R) domain (Riordan et al, 1989). The proper folding and assembly of CFTR subdomains in the endoplasmic reticulum (ER) is required for CFTR to engage the COPII machinery and be packaged into vesicles for transport to the plasma membrane (Kopito, 1999;Wang et al, 2004).…”