KChannelDB: Extraction of mutation data from the literature 2005, KChannelDB.
This data was extracted from Medline abstracts and full texts (when available) in an automated manner.
The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation L268I was found are listed after the table.
The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.
Point mutation L268I in IRK5_HUMAN
|General numbering (KChannelDB):|| -|
|Other point mutations / same protein||List of mutations in IRK5_HUMAN|
Inward rectifiers (Kir)|
Potassium channels 2 TMs
|Other point mutations / same position||
Position 243 in Inward rectifiers (Kir) family |
Position 243 in Potassium channels 2 TMs family
|Reference:||Identification of critical residues controlling G protein-gated inwardly rectifying K(+) channel activity through interactions with the beta gamma subunits of G proteins.|
He C, Yan X, Zhang H, Mirshahi T, Jin T, Huang A, Logothetis DE
J Biol Chem 2002 Feb 22;277(8):6088-96.
|Other point mutations / same article||List|
|Text source||HTML full text|
|Validation status||Not yet checked|
- Two of the 11 mutants , G4*(L268I) and G4*(A318C) , also abolished completely K + currents
- Again , the rescued G4*(I229L , L268I) and G4*(I229L , A318C) currents were convincingly above background (~4 ľA versus <0.5 ľA) and clearly inwardly rectifying (Fig. 4 C)
- Of these two C-terminal rescued mutants , the L268I currents were not significantly affected by beta ARK coexpression (Fig. 4 D)
- Thus , of the five non-functional mutants , one in the N terminus , G4*(H64F) , and one in the C terminus , G4*(L268I) , did not show inhibition by the G beta gamma sink , beta ARK-PH , suggesting that the His-64 and Leu-268 residues are critical for G beta gamma sensitivity
- Fig. 5 A shows that G1*(L262I) , the mutant corresponding to G4*(L268I) , greatly reduced but did not abolish basal G1* currents
- Fig. 5 B shows that the G1 / G4(H64F , L268I) heteromeric channels showed no activity , in contrast to the G1(H57F , L262I) / G4 channels that exhibited small inwardly rectifying K + currents
- When both mutant subunits were coexpressed , G1(H57F , L262I) and G4(H64F , L268I) , no K + currents could be measured
- The G4(L268I) / G1 showed greatly reduced currents
- Similarly , the only G4 mutant exhibiting channel activity when paired with the wild-type G1 (i.e. G1 / G4(L268I)) also showed clear heteromeric channel amplitude transitions (not shown)
- These results , taken together with the results of Fig. 5 C , suggest that the G4(H64F) mutant acted as a dominant negative in the heteromeric G1 / G4(H64F) channel , whereas the G4(L268I) mutant greatly reduced heteromeric G1 / G4(L268I) currents
- Because the G4(L268I) mutant did not but the G4(H64F) mutant did abolish basal currents when coexpressed with wild-type GIRK1 channels , it seems that the role of His-64 is more critical than Leu-268 in controlling heteromeric channel activity
- N- and C-terminal Point Mutations Reduce GIRK4 Channel Binding to the G beta gamma Subunits-- To test whether the H64F and L268I mutations affected channel binding to the G beta gamma subunits , we constructed and purified GST fusion proteins of the minimal G beta gamma -binding domains with or without the point mutations of interest , and then we tested their binding to purified G beta gamma subunits
- Both the H64F and the L268I mutations significantly reduced binding to G beta gamma of the N- and C-terminal binding fragments , respectively (Fig. 7 )
- Mutants H64F and L268I reduce G beta gamma binding to the channel
- Mutations of G beta gamma -interacting residues that abolished basal currents also showed no agonist-induced currents (e.g. GIRK4*(H64F) , GIRK4*(L268I) , or GIRK1*(H57F))
- Mutation of the two G beta gamma -interacting residues , GIRK4*(H64F) and GIRK4*(L268I) , abolished both basal and agonist-induced activities
F.Horn (kchanneldbcmbi.ru.nl), 17-Aug-2005