A specialized extracellular matrix of proteins and polysaccharides controls the morphology and packing of calcium carbonate crystals and becomes occluded within the mineralized composite during formation of the molluscan shell and pearl. We have cloned and characterized the cDNA coding for Lustrin A, a newly described matrix protein from the nacreous layer of the shell and pearl produced by the abalone, Haliotis rufescens, a marine gastropod mollusc. The full-length cDNA is 4,439 base pairs (bp) long and contains an open reading frame coding for 1,428 amino acids. The deduced amino acid sequence reveals a highly modular structure with a high proportion of Ser (16%), Pro (14%), Gly (13%), and Cys (9%). The protein contains ten highly conserved cysteine-rich domains interspersed by eight prolinerich domains; a glycine-and serine-rich domain lies between the two cysteine-rich domains nearest the C terminus, and these are followed by a basic domain and a C-terminal domain that is highly similar to known protease inhibitors. The glycine-and serine-rich domain and at least one of the proline-rich domains show sequence similarity to proteins of two extracellular matrix superfamilies (one of which also is involved in the mineralized matrixes of bone, dentin, and avian eggshell). The arrangement of alternating cysteine-rich domains and proline-rich domains is strikingly similar to that found in frustulins, the proteins that are integral to the silicified cell wall of diatoms. Its modular structure suggests that Lustrin A is a multifunctional protein, whereas the occurrence of related sequences suggest it is a member of a multiprotein family.The molluscan shell and pearl are mineralized structured composites of CaCO 3 crystals and organic polymers exhibiting exceptional nanoscale regularity and strength (1-14). Nacre, the lustrous material of pearl and the inner "mother of pearl" layers of many shells, exhibits a fracture toughness ϳ3,000 times greater than that of the mineral alone (15,16). Although the organic components typically constitute only ϳ1% by weight of the biomineralized composite material (17), they are responsible for its organization and the resulting enhancement of fracture toughness (3-7, 18 -21). Proteins represent the majority of extracellular organic polymers controlling biomineralization of the shell (8 -10); they comprise at least four functional classes, including (i) a nucleating sheet that participates in control of nucleation of the first layer of oriented calcite in deposition of the abalone shell and flat pearl (13, 14, 22), (ii) a family of polyanionic proteins that can be extracted by demineralization of the shell (8 -10, 17, 23-25) and have been shown in vitro to control the polymorph and atomic lattice orientation by cooperative interaction with the growing crystals (22,26,27), (iii) proteins of an insoluble, highly cross-linked matrix, forming an organizing network of interconnected compartments and fenestrated sheets that control the morphology and higher order packing of the CaCO 3 crys...