title: Determining the basis of channel-tetramerization specificity by x-ray crystallography and a sequence-comparison algorithm: Family Values (FamVal).
abstract: We have developed a semiempirical algorithm called Family Values (FamVal), which identifies residues that encode functional specificity in a protein sequence. Given a multiple sequence alignment (MSA) grouped into functionally distinct subfamilies, FamVal calculates a specificity score for each subfamily at every amino acid position of an MSA. This algorithm was used to predict specificity-encoding positions within the tetramerization assembly (T1) domain of voltage-gated potassium (Kv) channel subfamilies Kv3 and Kv4. The importance of one such position (Arg to Ala at MSA position 93) was confirmed by in vitro pull-down assays. The structural basis of this assembly discrimination was elucidated by determining the crystal structure of the Kv4 T1 domain and comparing it to the Kv3 T1 domain.
authors.affiliation: Structural Biology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Max H
authors.initials: MH
authors.lastname: Nanao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pfaffinger
authors.forename: Senyon
authors.initials: S
authors.lastname: Choe
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000235:genetics*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D051381:Rats; D016415:Sequence Alignment / Q000706:statistics & numerical data*; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels
chemical_list: D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels