Many investigations were conducted to characterize the cohesin-dockerin interactions. These studies include measuring cohesin-dockerin affinity, identifying critical amino acid residues by site-directed mutagenesis, and determining the molecular structures of the dockerin, cohesin, and its complex. Cohesins are highly conserved within the same scaffolding protein, with sequence identities higher than 50%. The interactions between the cohesin of the Clostridium thermocellum CipA scaffolding protein and the dockerin of cellulosomal catalytic components are categorized as type I, and the interactions between the dockerin of CipA and its counterpart are categorized as type II. The type I cohesins and dockerins include those modules from different microorganisms. This classification, however, is based on sequence homology and does not necessarily imply recognition among the same type of modules. Indeed, interspecies specificity was demonstrated using cohesins and dockerins from C. thermocellum and Clostridium cellulolyticum, respectively. In this work, Pages et al. found that C. thermocellum Cel48A (i.e., CelS), with its dockerin, did not recognize cohesin 1 of the C. cellulolyticum scaffolding protein CipC. The extremely high affinity between cohesin and dockerin and their important roles in cellulosome assembly have prompted interest in determining their molecular structures to elucidate the molecular mechanism of the cohesin-dockerin recognition. The first success in X-ray crystallography of a cohesin-dockerin complex was brought about by using a crystal of the dockerin of C. thermocellum Xyn10B and cohesin 2 of CipA, coexpressed in Escherichia coli and purified as a complex, yielding a good crystal suitable for X-ray analysis.