Lipid modification of the N-terminal Cys residue (N-acyl-S-diacylglyceryl-Cys) has been found to be an essential, ubiquitous, and unique bacterial posttranslational modification. Such a modification allows anchoring of even highly hydrophilic proteins to the membrane which carry out a variety of functions important for bacteria, including pathogenesis. Hence, being able to identify such proteins is of great value. To this end, we have created a comprehensive database of bacterial lipoproteins, called DOLOP, which contains information and links to molecular details for about 278 distinct lipoproteins and predicted lipoproteins from 234 completely sequenced bacterial genomes. The website also features a tool that applies a predictive algorithm to identify the presence or absence of the lipoprotein signal sequence in a user-given sequence. The experimentally verified lipoproteins have been classified into different functional classes and more importantly functional domain assignments using hidden Markov models from the SUPERFAMILY database that have been provided for the predicted lipoproteins. Other features include the following: primary sequence analysis, signal sequence analysis, and search facility and information exchange facility to allow researchers to exchange results on newly characterized lipoproteins. The website, along with additional information on the biosynthetic pathway, statistics on predicted lipoproteins, and related figures, is available at http://www.mrc-lmb.cam.ac.uk/genomes /dolop/.Essential cellular activities such as adhesion, digestion, transport, sensing, signal transduction, growth, and morphological changes such as spore formation in bacteria, etc., require a class of proteins, called membrane proteins, that work efficiently in aqueous environments while anchored to the hydrophobic membrane that envelops a cell. Organisms have evolved different strategies in the design of their membrane proteins, including the following: (i) transmembrane proteins, in which one or more peptide segments in their helical or beta sheeted structure traverse the width of the membrane to provide anchorage; the loops and parts of the transmembrane segments carry out the relevant function; (ii) proteins with a significant patch of hydrophobic surface which, along with other noncovalent and even ionic interactions, associate either loosely or tightly with the membrane; and (iii) covalent lipid modification of proteins, exo or endo, by fatty acids and other lipid moieties, which provide the hydrophobic anchor either at one end or on the surface of such proteins. The last strategy, particularly suited to hydrophilic proteins, is useful in engineering proteins for anchorage to hydrophobic surfaces.Bacteria, the major class among prokaryotes, possess an interesting N-terminal lipid modification, N-acyl-S-diacylglyceryl-Cys (Fig. 1A), which is unique and ubiquitous among its known members. More than 2,000 such proteins have been identified currently. Three fatty acyl groups at the N terminus which are derived from b...
