Evolutionary analysis reveals collective properties and specificity in the C-type lectin and lectin-like domain superfamily.

Members of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily share a common fold and are involved in a variety of functions, such as generalized defense mechanisms against foreign agents, discrimination between healthy and pathogen-infected cells, and endocytosis and blood coagulation. In this work we used ConSurf, a computer program recently developed in our lab, to perform an evolutionary analysis of this superfamily in order to further identify characteristics of all or part of its members. Given a set of homologous proteins in the form of multiple sequence alignment (MSA) and an inferred phylogenetic tree, ConSurf calculates the conservation score in every alignment position, taking into account the relationships between the sequences and the physicochemical similarity between the amino acids. The scores are then color-coded onto the three-dimensional structure of one of the homologous proteins. We provide here and at http://ashtoret.tau.ac.il/ approximately sharon a detailed analysis of the conservation pattern obtained for the entire superfamily and for two subgroups of proteins: (a) 21 CTLs and (b) 11 heterodimeric CTLD toxins. We show that, in general, proteins of the superfamily have one face that is constructed mostly of conserved residues and another that is not, and we suggest that the former face is involved in binding to other proteins or domains. In the CTLs examined we detected a region of highly conserved residues, corresponding to the known calcium- and carbohydrate-binding site of the family, which is not conserved throughout the entire superfamily, and in the CTLD toxins we found a patch of highly conserved residues, corresponding to the known dimerization region of these proteins. Our analysis also detected patches of conserved residues with yet unknown function(s).

Ebner S ，Sharon N ，Ben-Tal N 《-》

Comparative analysis of structural properties of the C-type-lectin-like domain (CTLD).

The superfamily of proteins containing the C-type-lectin-like domain (CTLD) is a group of abundant extracellular metazoan proteins characterized by evolutionary flexibility and functional versatility. Several CTLDs are also found in parasitic prokaryotes and viruses. The 37 distinct currently available CTLD structures demonstrate significant structural conservation despite low or undetectable sequence similarity. Our aim in this study was to perform an extensive comparative analysis of all available CTLD structures to establish the most conserved structural features of the fold, and to test and extend the early analysis of Drickamer. By implication, these features should be those critical for maintenance of integrity of the fold. By analyzing CTLD structures superimposed by several methods, we have established groups of conserved structural positions involved in fold maintenance but not in ligand binding; these are consistent with the fold's known functional flexibility. In addition to the well-recognized disulfide bridges, groups of conserved residues are involved in hydrophobic interactions stabilizing the core of the fold and the long loop region, and in an alpha2-beta1-beta5 polar interaction. Evaluation of the conclusions of the structure comparison study compared with alignments of all available human, mouse and Caenorhabditis elegans CTLD sequences showed that conservation patterns are preserved throughout the whole CTLD sequence space. Our observations provide an improved understanding of CTLD structure, and will help in identification of new CTLDs and the mechanisms that drive and constrain the coevolution of the structure and function of the fold.

Zelensky AN ，Gready JE 《-》

Cflec-4, a multidomain C-type lectin involved in immune defense of Zhikong scallop Chlamys farreri.

Zhang H ，Wang H ，Wang L ，Song L ，Song X ，Zhao J ，Li L ，Qiu L ... -  《-》

The ConSurf-HSSP database: the mapping of evolutionary conservation among homologs onto PDB structures.

The HSSP (Homology-Derived Secondary Structure of Proteins) database provides multiple sequence alignments (MSAs) for proteins of known three-dimensional (3D) structure in the Protein Data Bank (PDB). The database also contains an estimate of the degree of evolutionary conservation at each amino acid position. This estimate, which is based on the relative entropy, correlates with the functional importance of the position; evolutionarily conserved positions (i.e., positions with limited variability and low entropy) are occasionally important to maintain the 3D structure and biological function(s) of the protein. We recently developed the Rate4Site algorithm for scoring amino acid conservation based on their calculated evolutionary rate. This algorithm takes into account the phylogenetic relationships between the homologs and the stochastic nature of the evolutionary process. Here we present the ConSurf-HSSP database of Rate4Site estimates of the evolutionary rates of the amino acid positions, calculated using HSSP's MSAs. The database provides precalculated evolutionary rates for nearly all of the PDB. These rates are projected, using a color code, onto the protein structure, and can be viewed online using the ConSurf server interface. To exemplify the database, we analyzed in detail the conservation pattern obtained for pyruvate kinase and compared the results with those observed using the relative entropy scores of the HSSP database. It is reassuring to know that the main functional region of the enzyme is detectable using both conservation scores. Interestingly, the ConSurf-HSSP calculations mapped additional functionally important regions, which are moderately conserved and were overlooked by the original HSSP estimate. The ConSurf-HSSP database is available online (http://consurf-hssp.tau.ac.il).

Glaser F ，Rosenberg Y ，Kessel A ，Pupko T ，Ben-Tal N ... -  《-》

C-type lectin protein isoforms of Macrovipera lebetina: cDNA cloning and genetic diversity.

Jebali J ，Bazaa A ，Sarray S ，Benhaj K ，Karboul A ，El Ayeb M ，Marrakchi N ，Gargouri A ... -  《TOXICON》