The microbial degradation of cellulose is one of the most important processes on Earth, and it affects the human condition in many direct and indirect ways. If it did not occur, there would be an inexhaustible accumulation of plant cell refuse, and herbivorous life forms would largely vanish.The multienzyme cellulosome complex is a major mechanism by which some cellulolytic bacteria efficiently degrade cellulose and related plant cell wall polysaccharides (2,4,5,8,9,18,20,32,58,59). To date, cellulosomes have been found in several strains of anaerobic bacteria and fungi obtained from very different types of ecosystems. The first cellulosome was discovered in studies on the anaerobic thermophile Clostridium thermocellum (3,36,37). The cellulosome system of this organism consists of a variety of different enzymes bound to a noncatalytic scaffoldin subunit, which can, in turn, bind to one of several cell surface anchoring proteins. In this organism, both the attachment of the enzymes to the scaffoldin and the attachment of the scaffoldin to the anchoring proteins are accomplished by a special kind of protein-protein interaction, the cohesin-dockerin interaction. In this context, the enzyme subunits include a dockerin domain, and the scaffoldin contains multiple copies of cohesin modules for collective incorporation into the complex. The scaffoldin subunit itself harbors a single dockerin variant that interacts selectively with corresponding cohesin variants on the anchoring proteins. In C. thermocellum, the primary scaffoldin is trifunctional in that it also contains (in addition to the cohesins and dockerin) a substrate-targeting cellulose-binding domain (CBD). The anchoring proteins are bifunctional; in addition to the cohesins, they have another type of domain, the S-layer homology domain (SLH), which is known to bind strongly to the cell surface (12,40). Thus, the sequential cohesin-dockerin-mediated set of interactions among the enzymes, scaffoldin, and anchoring