title: Rampant exchange of the structure and function of extramembrane domains between membrane and water soluble proteins.
abstract: Of the membrane proteins of known structure, we found that a remarkable 67% of the water soluble domains are structurally similar to water soluble proteins of known structure. Moreover, 41% of known water soluble protein structures share a domain with an already known membrane protein structure. We also found that functional residues are frequently conserved between extramembrane domains of membrane and soluble proteins that share structural similarity. These results suggest membrane and soluble proteins readily exchange domains and their attendant functionalities. The exchanges between membrane and soluble proteins are particularly frequent in eukaryotes, indicating that this is an important mechanism for increasing functional complexity. The high level of structural overlap between the two classes of proteins provides an opportunity to employ the extensive information on soluble proteins to illuminate membrane protein structure and function, for which much less is known. To this end, we employed structure guided sequence alignment to elucidate the functions of membrane proteins in the human genome. Our results bridge the gap of fold space between membrane and water soluble proteins and provide a resource for the prediction of membrane protein function. A database of predicted structural and functional relationships for proteins in the human genome is provided at sbi.postech.ac.kr/emdmp.
authors.affiliation: Department of Life Science, Division of IT Convergence Engineering, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Nam
authors.forename: Seong Kyu
authors.initials: SK
authors.lastname: Han
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology; D030562:Databases, Protein; D056890:Eukaryota; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000032:analysis; D016415:Sequence Alignment; D012995:Solubility; D014867:Water
chemical_list: D008565:Membrane Proteins; D020543:Proteome; D014867:Water
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