Biomaterial Database

Probing the structural and functional domains of the CFTR chloride channel. 1997

M H Akabas, and M Cheung, and R Guinamard

Department of Physiology, Columbia University, New York, NY 10032, USA.

The cystic fibrosis transmembrane conductance regulator (CFTR) forms an anion-selective channel involved in epithelial chloride transport. Recent studies have provided new insights into the structural determinants of the channel's functional properties, such as anion selectivity, single-channel conductance, and gating. Using the scanning-cysteine-accessibility method we identified 7 residues in the M1 membrane-spanning segment and 11 residues in and flanking the M6 segment that are exposed on the water-accessible surface of the protein; many of these residues may line the ion-conducting pathway. The pattern of the accessible residues suggests that these segments have a largely alpha-helical secondary structure with one face exposed in the channel lumen. Our results suggest that the residues at the cytoplasmic end of the M6 segment loop back into the channel, narrowing the lumen, and thereby forming both the major resistance to ion movement and the charge-selectivity filter.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D017433	Protein Structure, Secondary	The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation.	Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein
D017434	Protein Structure, Tertiary	The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure.	Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D018118	Chloride Channels	Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.	CaCC,Calcium-Activated Chloride Channel,Chloride Ion Channel,Chlorine Channel,Ion Channels, Chloride,CaCCs,Calcium-Activated Chloride Channels,Chloride Channel,Chloride Ion Channels,Chlorine Channels,Ion Channel, Chloride,Calcium Activated Chloride Channel,Calcium Activated Chloride Channels,Channel, Calcium-Activated Chloride,Channel, Chloride,Channel, Chloride Ion,Channel, Chlorine,Channels, Calcium-Activated Chloride,Channels, Chloride,Channels, Chloride Ion,Channels, Chlorine,Chloride Channel, Calcium-Activated,Chloride Channels, Calcium-Activated
D018528	ATP-Binding Cassette Transporters	A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.	ABC Transporter,ABC Transporters,ATP-Binding Cassette Transporter,ATP Binding Cassette Transporter,ATP Binding Cassette Transporters,Cassette Transporter, ATP-Binding,Transporter, ABC,Transporter, ATP-Binding Cassette,Transporters, ABC,Transporters, ATP-Binding Cassette
D019005	Cystic Fibrosis Transmembrane Conductance Regulator	A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)	CFTR Protein,Chloride channels, ATP-gated CFTR,Chloride channels, ATP gated CFTR,Protein, CFTR