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Fibrillins and LTBPs [latent TGFβ (transforming growth factor β)-binding proteins] perform vital and complex roles in the extracellular matrix and are relevant to a wide range of human diseases. These proteins share a signature 'eight cysteine' or 'TB (TGFβ-binding protein-like)' domain that is found nowhere else in the human proteome, and which has been shown to mediate a variety of protein-protein interactions. These include covalent binding of the TGFβ propeptide, and RGD-directed interactions with a repertoire of integrins. TB domains are found interspersed with long arrays of EGF (epidermal growth factor)-like domains, which occur more widely in extracellular proteins, and also mediate binding to a large number of proteins and proteoglycans. In the present paper, newly available protein sequence information from a variety of sources is reviewed and related to published findings on the structure and function of fibrillins and LTBPs. These sequences give valuable insight into the evolution of TB domain proteins and suggest that the fibrillin domain organization emerged first, over 600 million years ago, prior to the divergence of Cnidaria and Bilateria, after which it has remained remarkably unchanged. Comparison of sequence features and domain organization in such a diverse group of organisms also provides important insights into how fibrillins and LTBPs might perform their roles in the extracellular matrix.

Original publication




Journal article


Biochem J

Publication Date





263 - 276


Animals, Evolution, Molecular, Fibrillins, Humans, Latent TGF-beta Binding Proteins, Microfilament Proteins, Protein Binding, Protein Structure, Tertiary