8xmo
Structural highlights
DiseaseSCN2B_HUMAN Familial atrial fibrillation. The disease is caused by mutations affecting the gene represented in this entry. Genetic variations in SCN2B may be involved in Brugada syndrome (PubMed:23559163). This tachyarrhythmia is characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.[1] FunctionSCN2B_HUMAN Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity). Publication Abstract from PubMedVoltage-gated sodium channels (Na(v)) undergo conformational shifts in response to membrane potential changes, a mechanism known as the electromechanical coupling. To delineate the structure-function relationship of human Na(v) channels, we have performed systematic structural analysis using human Na(v)1.7 as a prototype. Guided by the structural differences between wild-type (WT) Na(v)1.7 and an eleven mutation-containing variant, designated Na(v)1.7-M11, we generated three additional intermediate mutants and solved their structures at overall resolutions of 2.9-3.4 A. The mutant with nine-point mutations in the pore domain (PD), named Na(v)1.7-M9, has a reduced cavity volume and a sealed gate, with all voltage-sensing domains (VSDs) remaining up. Structural comparison of WT and Na(v)1.7-M9 pinpoints two residues that may be critical to the tightening of the PD. However, the variant containing these two mutations, Na(v)1.7-M2, or even in combination with two additional mutations in the VSDs, named Na(v)1.7-M4, failed to tighten the PD. Our structural analysis reveals a tendency of PD contraction correlated with the right shift of the static inactivation I-V curves. We predict that the channel in the resting state should have a "tight" PD with down VSDs. Dissection of the structure-function relationship of Na(v) channels.,Li Z, Wu Q, Huang G, Jin X, Li J, Pan X, Yan N Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2322899121. doi: , 10.1073/pnas.2322899121. Epub 2024 Feb 21. PMID:38381792[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||