The betagamma-crystallin superfamily comprises members from various taxa and species, which have similar domain topologies as that of lens beta- and gamma-crystallins. We have studied new microbial members of this understudied betagamma-crystallin superfamily from the bacterium Caulobacter crescentus. These proteins, which we named "caulollins", are paralogues with a single betagamma-crystallin domain, made up of two Greek key motifs with AB-type arrangement seen in gamma-crystallin. The second Greek key motif has Cys in place of a generally conserved Phe/Tyr residue, and the Tyr corner, considered important for the proper betagamma-crystallin fold, is missing, making this a sequentially diverse atypical betagamma-crystallin domain. This atypical domain binds two Ca2+ with moderate affinity (0.8-20 microM). In apo form, caulollins are partially unstructured proteins and gain structure upon binding Ca2+. Unlike many other microbial betagamma-crystallin domains, this domain is monomeric, though in the presence of Ca2+ it becomes more compact. Ca2+ binding increases the intrinsic stability of proteins, suggesting the role of Ca2+ as an extrinsic stabilizer. N-Terminal extension does not play any role in modulating Ca2+ binding, intrinsic stability, or oligomerization. We noted that there are several such variant domains in the genomes of unrelated species. It appears that caulollins along with these members form a subfamily in the betagamma-crystallin superfamily that would be partially unstructured in apo form, unlike many other domains from lens or microbial crystallins. This work further suggests that Ca2+ binding is a widespread feature of the betagamma-crystallin superfamily.