title: Current status of membrane protein structure classification.
abstract: For over 2 decades, continuous efforts to organize the jungle of available protein structures have been underway. Although a number of discrepancies between different classification approaches for soluble proteins have been reported, the classification of membrane proteins has so far not been comparatively studied because of the limited amount of available structural data. Here, we present an analysis of alpha-helical membrane protein classification in the SCOP and CATH databases. In the current set of 63 alpha-helical membrane protein chains having between 1 and 13 transmembrane helices, we observed a number of differently classified proteins both regarding their domain and fold assignment. The majority of all discrepancies affect single transmembrane helix, two helix hairpin, and four helix bundle domains, while domains with more than five helices are mostly classified consistently between SCOP and CATH. It thus appears that the structural constraints imposed by the lipid bilayer complicate the classification of membrane proteins with only few membrane-spanning regions. This problem seems to be specific for membrane proteins as soluble four helix bundles, not restrained by the membrane, are more consistently classified by SCOP and CATH. Our findings indicate that the structural space of small membrane helix bundles is highly continuous such that even minor differences in individual classification procedures may lead to a significantly different classification. Membrane proteins with few helices and limited structural diversity only seem to be reasonably classifiable if the definition of a fold is adapted to include more fine-grained structural features such as helix-helix interactions and reentrant regions.
authors.affiliation: Department of Genome Oriented Bioinformatics, Technische Universität München, Wissenschaftszentrum Weihenstephan, D-85354 Freising, Germany.
authors.forename: Sindy
authors.initials: S
authors.lastname: Neumann
authors.forename: Angelika
authors.initials: A
authors.lastname: Fuchs
authors.forename: Armen
authors.initials: A
authors.lastname: Mulkidjanian
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Frishman
mesh_terms: D030562:Databases, Protein; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D008958:Models, Molecular; D015221:Potassium Channels; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D008565:Membrane Proteins; D015221:Potassium Channels