Insights into the quaternary association of proteins through structure graphs: a case study of lectins

Abstract

The unique three-dimensional structure of both monomeric and oligomeric proteins is encoded in their sequence. The biological functions of proteins are dependent on their tertiary and quaternary structures, and hence it is important to understand the determinants of quaternary association in proteins. Although a large number of investigations have been carried out in this direction, the underlying principles of protein oligomerization are yet to be completely understood. Recently, new insights into this problem have been gained from the analysis of structure graphs of proteins belonging to the legume lectin family. The legume lectins are an interesting family of proteins with very similar tertiary structures but varied quaternary structures. Hence they have become a very good model with which to analyse the role of primary structures in determining the modes of quaternary association. The present review summarizes the results of a legume lectin study as well as those obtained from a similar analysis carried out here on the animal lectins, namely galectins, pentraxins, calnexin, calreticulin and rhesus rotavirus Vp4 sialic-acid-binding domain. The lectin structure graphs have been used to obtain clusters of non-covalently interacting amino acid residues at the intersubunit interfaces. The present study, performed along with traditional sequence alignment methods, has provided the signature sequence motifs for different kinds of quaternary association seen in lectins. Furthermore, the network representation of the lectin oligomers has enabled us to detect the residues which make extensive interactions ('hubs') across the oligomeric interfaces that can be targetted for interface-destabilizing mutations. The present review also provides an overview of the methodology involved in representing oligomeric protein structures as connected networks of amino acid residues. Further, it illustrates the potential of such a representation in elucidating the structural determinants of protein-protein association in general and will be of significance to protein chemists and structural biologists.

Structure of the Mouse Peptide N-Glycanase-HR23 Complex Suggests Co-evolution of the Endoplasmic Reticulum-associated Degradation and DNA Repair Pathways

“…The first consists of homologous proteins with different quaternary structures, such as globins (49) and lectins (50). These proteins have conserved tertiary structures; however, utilizing different types of protein contacts, they can assemble into a variety of quaternary states, from dimers to oligomers containing as many as 144 subunits as in the case of Lumbricus terrestris erythrocruorin (51).…”

Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces

“…It is reported that the formation of different PTX quaternary structures is due to differences in interface residues. For instance, the interface sites of decameric frog PTX are different from those of pentameric human PTXs (Brinda et al, 2005). According to the sequence comparison among hCRP, hSAP, reported pentameric fish PTXs and Dare-CRP, conserved interface sites such as Lys119 (in hCRP) are observed in pentameric PTXs.…”

A New Approach to Inhibit Prototypic Galectins

“…How lectins form homodimers has been the subject of intense research. In some cases, such as plant lectins, specific signature sequences have been identified to explain the different modes of association implicated in the formation of homodimers (69). Each human galectin has its own sequence signature, which excludes most of the residues found in the signature sequence of the plant lectin interface.…”