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 E283H 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 E283H in KCAB2_HUMAN
- E283Q / R371H Channel There is evidence for the existence of charged networks between acidic residues in the S2 and S3 transmembrane segments and some of the basic residues in S4 (Tiwari-Woodruff et al. 1997 (image) , Tiwari-Woodruff et al. 2000 (image) )
- One such network contains three participants: R368 and R371 in S4 and E283 in S2
- Interaction between these residues has been demonstrated by the necessity to pair neutralization of residue E283 with neutralization of either R368 or R371 to obtain functional channels (Tiwari-Woodruff et al. 1997 (image) )
- Neutralization of the S2 residue (E283) in the R368H and R371H channels provides an effective way to examine residue 283's effect on the accessibility of residues 368H and 371H in both charged and uncharged states
- Addition of the neutralizing mutation , E283Q , to the R371H channel slowed the gating current kinetics by ~10-fold (Fig 12 A)
- The asymmetry of charge displacement created by a pH gradient demonstrates that even when E283 is neutralized , the histidine at position 371 passes from internal to external accessibility with each voltage sensor transition from the hyperpolarized to depolarized state
- Gating currents of the E283Q / R371H channel
- (A) Using the cut-open oocyte voltage clamp , E283Q / R371H channel gating currents were measured in symmetric NMDG-MS solutions with internal pH 9.2 , and either pH o 9.2 (top currents) or pH o 5 (bottom currents)
- (Experiment D11037a) Since E283Q / R371H channel charge displacement is asymmetric in a pH gradient , a proton current should accompany each voltage sensor stroke
- The properties of the steady-state ON-gating currents of the E283Q / R371H channel resemble those of the R371H channel in many respects except one: the sizes of the proton currents are dramatically reduced
- The steady-state ON-gating currents from the E283Q / R371H channel are barely above the background , making it difficult to attribute them to something as specific as proton transport and / or conduction by the histidine at position 371
- The slow kinetics of the E283Q / R371H channel gating currents indicate slow voltage sensor transitions
- Alternatively , the reduction of proton current amplitudes through a pore formed by 371H could be due to the disruption of proton selectivity by E283 neutralization
- Since positions 371 and 283 interact in depolarized states (Tiwari-Woodruff et al. 2000 (image) ) , neutralization of E283 could very likely perturb the 371H pK a while in a pore-forming state
- If , in the depolarized state , E283 decreases the local external pH around 371H relative to the bulk , then neutralization of E283 would effectively lower the external pK a of the proton pore
- If external proton access to the 371H pore is through a narrow , nonisopotential cavity , then E283 neutralization may alter the electric field drop through the cavity , and thereby alter the effective external pK a of the pore
- These are just a couple of the many ways that E283 neutralization could affect the 371H pK a and cause a reduction of proton current through a pore formed by 371H
- The reduction of E283Q / R371H channel proton current amplitudes is consistent with both transport and pore formation by 371H
- Although E283Q neutralization makes no progress in determining the composition of R371H proton currents , it does suggest some interesting ways of designing effective proton pores
- There is evidence that residue R368 in S4 also interacts with E283 (Tiwari-Woodruff et al. 1997 (image) , Tiwari-Woodruff et al. 2000 (image) )
- However , addition of the neutralizing mutation (E283Q) to the R368H channel did not alter the gating or proton transport properties of the channel at all (data not shown)
F.Horn (kchanneldbcmbi.ru.nl), 17-Aug-2005