Silicatein α exists within the protein filament of silica spicules of the marine sponge Tethya aurantium in a predominantly β-sheet structure. However, it is produced in a soluble form with mixed α-helix/β-sheet structure akin to its cathepsin L homologue. To understand this conformational transition in the context of enzyme catalyzed silica condensation, we used a functional, recombinant silicatein α termed 4SER. In solution, 4SER becomes conformationally unstable at pH 7 and readily unfolds to a soluble β-sheet intermediate, losing the majority of its helical structure. This β-sheet intermediate is present following adsorption of 4SER to a silica surface from solution. 4SER is particularly surface active, forming a near saturated monolayer on SiO2 from low bulk concentrations, without transition to multilayers at high bulk concentrations. The adsorbed intermediate remains stable during silica condensation and drying. We propose that the β-sheet structure for silicatein α in marine sponge spicules represents a stable structural intermediate, formed upon adsorption to the silica surface.