GTPase HRas: Difference between revisions
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<applet load='5p21' size='450' frame='true' align='right' caption='RAS Superfamily'/> | <applet load='5p21' size='450' frame='true' align='right' caption='RAS Superfamily'/> | ||
The ''RAS'' gene family was discovered due to the presence of two closely related retroviral cancer genes (oncogenes) | [[Image:Hras.png|150px|left]] The ''RAS'' gene family was discovered due to the presence of two closely related retroviral cancer genes (oncogenes) | ||
within the Harvey and Kirsten '''RA'''t '''S'''arcoma viruses. These retroviral oncogenes arose via capture of two normal cellular genes, ''H-RAS'' and ''K-RAS''. A DNA transfection assay for oncogenes in human bladder cancer later identified the same ''H-RAS'' gene. Remarkably, the mutated oncogenic form of ''H-RAS'' differed from its normal counterpart by a single nucleotide change that caused a single amino acid substitution. Biochemical studies of purified RAS proteins revealed that they were capable of binding nucleotides, with a particularly high affinity for GTP. Extensive genetic, biochemical, and structural studies have established a model in which the RAS proteins function as molecular switches, as do related GTP-binding proteins. The RAS switch is "ON" when it binds <scene name='User:Joseph_Lipsick/RAS/Ras-gtp_switches/5'>GTP</scene>, and is "OFF" when it binds <scene name='User:Joseph_Lipsick/RAS/Ras-gdp_switches/11'>GDP</scene>. The changes in protein conformation between the <scene name='User:Joseph_Lipsick/RAS/Ras-gtp_switch_i_ii_spacefill/2'>"ON"</scene> and <scene name='User:Joseph_Lipsick/RAS/Ras-gdp_switch_i_ii_spacefill/3'>"OFF"</scene> states are not very large. These changes primarily occur in two regions known as SWITCH I (yellow) and SWITCH II (magenta), and can be visualized by toggling the spin off and on in these partial space-filling models. The RAS protein itself has an intrinsic GTPase activity, thereby limiting the duration of time spent in the "ON" configuration. | within the Harvey and Kirsten '''RA'''t '''S'''arcoma viruses. These retroviral oncogenes arose via capture of two normal cellular genes, ''H-RAS'' and ''K-RAS''. A DNA transfection assay for oncogenes in human bladder cancer later identified the same ''H-RAS'' gene. Remarkably, the mutated oncogenic form of ''H-RAS'' differed from its normal counterpart by a single nucleotide change that caused a single amino acid substitution. Biochemical studies of purified RAS proteins revealed that they were capable of binding nucleotides, with a particularly high affinity for GTP. Extensive genetic, biochemical, and structural studies have established a model in which the RAS proteins function as molecular switches, as do related GTP-binding proteins. The RAS switch is "ON" when it binds <scene name='User:Joseph_Lipsick/RAS/Ras-gtp_switches/5'>GTP</scene>, and is "OFF" when it binds <scene name='User:Joseph_Lipsick/RAS/Ras-gdp_switches/11'>GDP</scene>. The changes in protein conformation between the <scene name='User:Joseph_Lipsick/RAS/Ras-gtp_switch_i_ii_spacefill/2'>"ON"</scene> and <scene name='User:Joseph_Lipsick/RAS/Ras-gdp_switch_i_ii_spacefill/3'>"OFF"</scene> states are not very large. These changes primarily occur in two regions known as SWITCH I (yellow) and SWITCH II (magenta), and can be visualized by toggling the spin off and on in these partial space-filling models. The RAS protein itself has an intrinsic GTPase activity, thereby limiting the duration of time spent in the "ON" configuration. | ||