Recent studies indicate that the ability of mollusk shell nacre protein sequences to form the calcium carbonate polymorph, aragonite, are linked to the presence of intrinsically disordered sequences within these proteins. Although the exact relationship between protein structural disorder and polymorph formation is not clear, there is a definite interest in discovering other examples of intrinsically disordered nacre protein sequences that can induce aragonite formation. In this report, we extend the relationship between intrinsic disorder and aragonite formation to another set of nacre protein sequences. This protein, known as PFMG1, is associated with pearl formation in the Japanese pearl oyster, Pinctada fucata. We demonstrate that synthetic peptides representing the 30 AA N-and C-terminal sequence regions of PFMG1 nucleate nanoscale-sized aragonite in solution without the need for additional additives. Compared to controls containing no peptide or bovine serum albumin, the PFMG1 terminal sequences appear to form a matrix-like environment around the forming biominerals, and this process will be defined in more detail in later reports. Furthermore, we establish that these PFMG1 terminal sequences possess disordered structures in solution that can be stabilized into partially folded structures (R helix, beta structures) using the structure-stabilizing solvent, 2,2,2-trifluoroethanol. Although we do not know the mechanism by which these peptides promote aragonite nucleation in vitro, we believe that these terminal sequences are participants in PFMG1-mediated aragonite polymorph formation within the oyster pearl and that the intrinsic disorder and folding propensities of these sequences are crucial for this activity.The mollusk shell is a biocomposite that is comprised of two distinct layers of calcium carbonate that coexist with a series of biomacromolecules. [1][2][3][4][5][6][7][8][9][10][11] One of these layers, known as the nacre layer, is comprised of the calcium carbonate polymorph, aragonite, which is thermodynamically unstable. 4 Moreover, the nacre layer is fracture-resistant (3000Â greater than pure aragonite) 5 and under force stress exhibits crack deflection and energy dissipation. [6][7][8] These material properties arise from the presence of proteins which inhabit the aragonite crystals (intercalation or occlusion) 9 and the space surrounding these crystals. [1][2][3] Interestingly, these same proteins may play a role in the nucleation of aragonite [1][2][3]9 and the formation of an amorphous precursor, amorphous calcium carbonate (ACC). 1,12 Hence, the nacre layer represents an important model system for extracting molecular principles (nucleation, protein occlusion, fracture toughness) that Nature uses to create composite materials under ambient conditions.One molecular principle that appears to emerge is the link between disordered protein structure and biomineralization protein function. Recently, a nacre protein, AP7 (Haliotis rufescens), was found to stabilize single and polycrystalline aragon...