Protein-protein interactions regulate and drive biological processes and understanding the assembly of these interactions is important. The LysR-Type Transcriptional Regulators (LTTRs) are a large family of transcriptional regulators found in prokaryotes. I have used the LTTRs as a model for protein specificity. In order to understand a residue's contribution to oligomerization, alanine-scanning mutagenesis was used to probe the contribution of residues identified from in silico analysis of two proteins: OxyR and CynR. The contribution of the residues to oligomerization was characterized using λcI repressor fusions. In OxyR, seven residues were identified as hot spots. Moreover, these hot spots are not especially conserved. The interaction surface of OxyR was mapped onto a multiple sequence alignment of the LTTR family. This mapping identified putative contacts in the CynR regulatory domain dimer interface. Combined with the in vivo testing, three residues were identified as hot spots. The residues identified in OxyR and CynR do not overlap. To investigate the assembly of the LTTRs I used a negative-dominance assay with λcI repressor fusions. Taken together, I show that the LTTRs in E. coli K-12 are mostly specific in their interactions.