struct.calcsize('iiiii?') : 21

appears to be incorrect ; in C sizeof : 24

C code:
typedef struct {
  int	param1;
  int	param2;
  int	param3;
  int	param4;
  int	param5;
  unsigned char param6;
} struct_titi6;

main:
struct_titi6 toto3;
printf("taille toto3 : %d\n",sizeof(toto3));
printf("taille toto3.param1 : %d\n",sizeof(toto3.param1));
printf("taille toto3.param6 : %d\n",sizeof(toto3.param6));

results:
taille toto3 : 24
taille toto3.param1 : 4
taille toto3.param6 : 1

This is working as designed: the result of struct.calcsize matches the length of the string that you'll get back from struct.pack using that format.  Padding isn't included after the last entry in the struct.

That's not to say that it was a good design decision, but that's the design that was chosen, and it's not realistic to change this for the bugfix releases.  It may be possible to do something for Python 3.4.

You can add a '0L' to the end of your struct to force padding bytes at the end.  See:

http://docs.python.org/2/library/struct.html#examples

for an example of this.

See also #7189, #5145.

And also #7355, which led to that example being added to the documentation.  Closing as duplicate.