title: Distribution and function of new bacterial intein-like protein domains.
abstract: Hint protein domains appear in inteins and in the C-terminal region of Hedgehog and Hedgehog-like animal developmental proteins. Intein Hint domains are responsible and sufficient for protein-splicing of their host-protein flanks. In Hedgehog proteins the Hint domain autocatalyses its cleavage from the N-terminal domain of the Hedgehog protein by attaching a cholesterol molecule to it. We identified two new types of Hint domains. Both types have active site sequence features of Hint domains but also possess distinguishing sequence features. The new domains appear in more than 50 different proteins from diverse bacteria, including pathogenic species of humans and plants, such as Neisseria meningitidis and Pseudomonas syringae. These new domains are termed bacterial intein-like (BIL) domains. Bacterial intein-like domains are present in variable protein regions and are typically flanked by domains that also appear in secreted proteins such as filamentous haemagglutinin and calcium binding RTX repeats. Phylogenetic and genomic analysis of BIL sequences suggests that they were positively selected for in different lineages. We cloned two BIL domains of different types and showed them to be active. One of the domains efficiently cleaved itself from its C-terminal flank and could also protein-splice its two flanks, in E. coli and in a cell free system. We discuss several possible biological roles for BIL domains including microevolution and post translational modification for generating protein variability.
authors.affiliation: Molecular Genetics Department and Mass Spectrometry Unit, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Amitai
authors.forename: Olga
authors.initials: O
authors.lastname: Belenkiy
authors.forename: Bareket
authors.initials: B
authors.lastname: Dassa
authors.forename: Alla
authors.initials: A
authors.lastname: Shainskaya
authors.forename: Shmuel
authors.initials: S
authors.lastname: Pietrokovski
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D015870:Gene Expression; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D019154:Protein Splicing / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology*; D011549:Pseudomonas / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins