Structure and Function of the Py-Complex

Structures of the ySy-complex could be obtained both in the free state and in the Ga-GDP-bound state. The /ip-complex has an interesting configuration of seven /1-sheet structures for the y3-subunit. This configuration is called WD repeat or -propeller structure because it has the form of a propellor with seven configured leaves and contains repeats of the dipeptide WD. The WD repeat motif is found in a large number of proteins and is considered a to be a stable platform that can reversibly form complexes with other proteins. 

Along the GTPase cycle, the / y-complex contacts at least three types of signaling proteins the Ga-subunit, the activated receptor and the ySy-specific effector proteins. 

Contacts to Ga are mediated only via the y3-subunit, which binds in the region of the switch regions I and II and in the region of the N-terminus of the a-subunit. The binding to switches I and II ofthe a-subunit masks interaction sites for downstream effector proteins and prevents transmission of a signal in the ground state. The y-sub-unit is located at the side of the /1-subunit and does not itself interact with the a-sub-unit. Rather, the y-subunit seems to be involved in the interaction with the activated receptor via its farnesylated C-terminus. 

Mutational analysis has revealed the structural elements of the /fy-complex that interact with the effectors (Ford et al., 1998). The interaction sites with different effectors overlap partially and are only available for binding in the absence of the a-subunit. This organization of the interaction regions allows the key regulator Ga to control G/u signal transmission to multiple effectors. 

Originally, it was assumed that the /fy-complex only played a passive role in the functional cycle of the G proteins. It soon became apparent, however, that the fly-com-plex, in addition to binding to the a-subunit, also carries out other functions and interacts specifically with corresponding effector molecules. The /fy-complex must be assigned its own regulatory Junction it takes part itself in the propagation and termination of signal transmission. 

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