Determining the basis of channel-tetramerization specificity by x-ray crystallography and a sequence-comparison algorithm: Family values (FamVal)
- 30 June 2003
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 100 (15) , 8670-8675
- https://doi.org/10.1073/pnas.1432840100
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.Keywords
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