Deficiency of propionyl-CoA carboxylase (PCC; alpha 4 beta 4) results in the 
rare, autosomal recessive disease propionic acidemia. Cell fusion experiments 
have revealed two complementation groups, pccA and pccB, corresponding to 
defects of the PCCA (alpha-subunit) and PCCB (beta-subunit) genes, respectively. 
The pccBCC group includes subgroups, pccB and pccC, which are thought to reflect 
interallelic complementation between certain mutations of the PCCB gene. In this 
study, we have identified the mutations in two pccB, one pccC, and two pccBC 
cell lines and have deduced those alleles participating in interallelic 
complementation. One pccB line was a compound heterozygote of Pro228Leu and 
Asn536Asp. The latter mutation was also detected in a noncomplementing pccBC 
line. This leaves Pro228Leu responsible for complementation in the pccB cells. 
The second pccB line contained an insertional duplication, dupKICK140-143, and a 
splice mutation IVS + 1 G-->T, located after Lys466. We suggest that the dupKICK 
mutation is the complementing allele, since the second allele is incompatible 
with normal splicing. The pccC line studied was homozygous for Arg410Trp, which 
is necessarily the complementing allele in that line. For a second pccC line, we 
previously had proposed that delta Ile408 was the complementing allele. We now 
show that its second allele, "Ins.Del," a 14-bp deletion replaced by a 12-bp 
insertion beginning at codon 407, fails to complement in homozygous form. We 
conclude that the interallelic complementation results from mutations in domains 
that can interact between beta-subunits in the PCC heteromer to restore 
enzymatic function. On the basis of sequence homology with the Propionibacterium 
shermanii transcarboxylase 12S subunit, we suggest that the pccC domain, defined 
by Ile408 and Arg410, may involve the propionyl-CoA binding site.