You can install one slot of 4gB if your motherboard supports a 4gB cards, I guess your motherboard is lga 775 or earlier there may be a slim chance of 4gB support but then again you can always check it. It should be highligted in your motherboard manual
Another thing is that if are placing different cards together then it might crash randomly.
Check the memory speed of the new stick matches the memory speed currently in the system, make sure the new stick has the same voltage required to run it as the old memory.
One of the problems you may have if you have two sticks of memory in two slots and then put the 4gb stick in just one slot is the mode the memory will want to work at you may go from dual channel memory to single channel memory mode. And as said check that the single memory slot will support a max size of a 4gb capacity memory stick.
I try to not minx'n'match RAM. I always use the same quantity with the same voltage/clockspeed. For instance:
2 x 4GB DDR3 or 4 x 2GB DDR3
I try not to do:
1 x 4GB DDR3 AND 2 x 2GB DDR3
I'm not sure if the memory size would effect this, but the clock speeds and voltage can vary between RAM modules. From what I have heard it can damage your motherboard/RAM or the RAM will generally just act slower. You can try to get more RAM, but get more that has the same clock speed and voltage.
Also, if your motherboard is DDR3 it should support 1 x 4GB Ram, however if it is DDR2 or DDR, I am not sure. I know DDR only supports 2GB and below. (I could never find a 4GB RAM Module for that.)