A new method for comparing and aligning protein sequences is described. This method, hydrophobic cluster analysis (HCA), relies upon a two-dimensional (2D) representation of the sequences. Hydrophobic clusters are determined in this 2D pattern and then used for the sequence comparisons. The method does not require powerful computer resources and can deal with distantly related proteins, even if no 3D data are available. This is illustrated in the present report by a comparison of human haemoglobin with leghaemoglobin, a comparison of the two domains of liver rhodanese (thiosulphate sulphurtransferase) and a comparison of plastocyanin and azurin.

C1q is a versatile recognition protein that binds to an amazing variety of immune and non-immune ligands and triggers activation of the classical pathway of complement. The crystal structure of the C1q globular domain responsible for its recognition properties has now been solved and refined to 1.9 Å of resolution. The structure reveals a compact, almost spherical heterotrimeric assembly held together mainly by non-polar interactions, with a Ca 2؉ ion bound at the top. The heterotrimeric assembly of the C1q globular domain appears to be a key factor of the versatile recognition properties of this protein. Plausible three-dimensional models of the C1q globular domain in complex with two of its physiological ligands, C-reactive protein and IgG, are proposed, highlighting two of the possible recognition modes of C1q. The C1q/human IgG1 model suggests a critical role for the hinge region of IgG and for the relative orientation of its Fab domain in C1q binding.Innate immunity involves a combination of cell-surface receptors and soluble proteins with the ability to recognize microbial pathogens and thereby to generate signals that both orientate subsequent adaptive immune responses and trigger effector mechanisms (1, 2). Most of these molecules are oligomeric and recognize molecular patterns on microorganisms (3). An archetypal molecule of this type is C1q, the recognition subunit of C1, the complex that triggers activation of the classical pathway of complement, a major element of innate immunity. C1q is a 460-kDa protein with the overall shape of a bouquet of flowers, comprising six heterotrimeric collagen-like triple helices that associate in their N-terminal half to form a "stalk," then diverge to form individual "stems", each terminating in a C-terminal heterotrimeric globular domain (4). It is well documented that most of the C1 complex ligands are recognized by these peripheral globular domains, or heads, of C1q, thus triggering activation of C1r and C1s, the proteases associated with C1q (5). It is also established that C1q binds to immune complexes containing IgG or IgM, but not to those having IgA, IgD, or IgE (6). The major C1q binding site on IgG has been mapped to the CH2 domain of the Fc portion of the molecule (7-9). Although C1q shows marked differences in its reactivity toward IgG subclasses, the reason for this selectivity is not known.C1q is traditionally known for its ability to bind antibodies. However, it recognizes an amazing variety of other ligands. These include certain bacteria, viruses, parasites, and mycoplasma (6, 10 -12), underscoring its role as an antibody-independent defense protein. C1q also binds to C-reactive protein (CRP) 1 when complexed with exposed phosphocholine residues on bacteria, providing a further means of host defense (13). C1q is also capable of recognizing aberrant structures from self. Thus, in addition to cellular debris and sub-cellular membranes (14), it is established that C1q binds to, and induces clearance of, apoptotic cells (15), thereby playing a major role ...

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