课件分子医学structural biology-32011.3.pptxVIP

Application examples;Structural Study of Ion Channel Selectivity and Gating;;K+ Channel Selectivity;;;What are the structural bases for these characteristics?;;;N;;How many ions are there in the filter;;;=;;High [K+];Conclusions from MacKinnon’s studies:;Kv2.1 K+ channel conducts Na+ in a K+-free conditionKorn and Ikeda, Science 1995;Kv2.1 K+ channel displays anomalous mole fraction behavior in mixtures of Na+ and K+Korn and Ikeda, Science 1995;Questions;MthK is a Ca2+-gated K+ channel from Methanobacterium thermoautotrophicum ;;The selectivity filter of MthK is identical to that of KcsA;The selectivity filter of MthK channel maintains the same conformation in different conditions;MthK K+ channel can conduct Na+ with much small conductance in the K+-free condition!;MthK K+ channel displays anomalous mole fraction behavior in mixtures of Na+ and K+;Exactly how many K+ ions occupy the four ion-binding sites in the MthK selectivity filter in the low K+/high Na+ condition? How do these K+ ions distribute in the selectivity filter in the low K+/high Na+ condition?;Anomalous signal of the K+ ions and S atoms from MthK pore crystal is strong enough;Anomalous signal from K+ ions provides the structural basis for the anomalous mole-fraction behavior;Summary;The Central Question in ion selectivity: ;NaK channel ? a Na+ and K+ -conducting channel;NaK is a Homolog of Cyclic Nucleotide-Gated Channel Pore;3.5 ?, FOM=0.26;;Structures of NaK in complexed with Na+ or K+;;2Fo-Fc map Fo-Fc ion omit map;;;NaK channel conducts both Na+ and K+, and might represent the pore of a CNG channel. NaK channel shares the same overall architecture as a K+ channel pore. NaK channel preserves half of the ion binding sites, but replaces the other half with a vestibule. Ca2+ or Mg2+ blocks NaK conduction by binding at the external entrance to the filter.;K+ Channel Gating;;Closed Opened;The Central Question in ligand-gating: ;Structural and functional studies on C