References of "Amoros, Dolors"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailResidues crucial for maintaining short paths in network communication mediate signaling in proteins
del Sol Mesa, Antonio UL; Fujihashi, Hirotomo; Amoros, Dolors et al

in Molecular Systems Biology (2009), 2

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flowof information between amino acids. By removal of nodes from the protein network, we ... [more ▼]

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flowof information between amino acids. By removal of nodes from the protein network, we identify fold centrally conserved residues, which are crucial for sustaining the shortest pathways and thus play key roles in long-range interactions. Analysis of seven protein families (myoglobins, G-protein-coupled receptors, the trypsin class of serine proteases, hemoglobins, oligosaccharide phosphorylases, nuclear receptor ligand-binding domains and retroviral proteases) confirms that experimentally many of these residues are important for allosteric communication. The agreement between the centrally conserved residues, which are key in preserving short path lengths, and residues experimentally suggested to mediate signaling further illustrates that topology plays an important role in network communication. Protein folds have evolved under constraints imposed by function. To maintain function, protein structures need to be robust to mutational events. On the other hand, robustness is accompanied by an extreme sensitivity at some crucial sites. Thus, here we propose that centrally conserved residues, whose removal increases the characteristic path length in protein networks, may relate to the system fragility. [less ▲]

Detailed reference viewed: 120 (2 UL)
Peer Reviewed
See detailModular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages.
del Sol Mesa, Antonio UL; Arauzo-Bravo, Marcos J.; Amoros, Dolors et al

in Genome biology (2007), 8(5), 92

BACKGROUND: Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. RESULTS: We show that ... [more ▼]

BACKGROUND: Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. RESULTS: We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Galphas subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization. CONCLUSION: Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages. [less ▲]

Detailed reference viewed: 96 (0 UL)
Peer Reviewed
See detailResidue centrality, functionally important residues, and active site shape: analysis of enzyme and non-enzyme families.
del Sol Mesa, Antonio UL; Fujihashi, Hirotomo; Amoros, Dolors et al

in Protein science : a publication of the Protein Society (2006), 15(9), 2120-8

The representation of protein structures as small-world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the ... [more ▼]

The representation of protein structures as small-world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the performance of residue centrality, viewed as a family fold characteristic, in identifying functionally important residues in protein families. Our study is based on 46 families, including 29 enzyme and 17 non-enzyme families. A total of 80% of these central positions corresponded to active site residues or residues in direct contact with these sites. For enzyme families, this percentage increased to 91%, while for non-enzyme families the percentage decreased substantially to 48%. A total of 70% of these central positions are located in catalytic sites in the enzyme families, 64% are in hetero-atom binding sites in those families binding hetero-atoms, and only 16% belong to protein-protein interfaces in families with protein-protein interaction data. These differences reflect the active site shape: enzyme active sites locate in surface clefts, hetero-atom binding residues are in deep cavities, while protein-protein interactions involve a more planar configuration. On the other hand, not all surface cavities or clefts are comprised of central residues. Thus, closeness centrality identifies functionally important residues in enzymes. While here we focus on binding sites, we expect to identify key residues for the integration and transmission of the information to the rest of the protein, reflecting the relationship between fold and function. Residue centrality is more conserved than the protein sequence, emphasizing the robustness of protein structures. [less ▲]

Detailed reference viewed: 114 (0 UL)
Peer Reviewed
See detailResidues crucial for maintaining short paths in network communication mediate signaling in proteins.
del Sol Mesa, Antonio UL; Fujihashi, Hirotomo; Amoros, Dolors et al

in Molecular systems biology (2006), 2

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flow of information between amino acids. By removal of nodes from the protein network, we ... [more ▼]

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flow of information between amino acids. By removal of nodes from the protein network, we identify fold centrally conserved residues, which are crucial for sustaining the shortest pathways and thus play key roles in long-range interactions. Analysis of seven protein families (myoglobins, G-protein-coupled receptors, the trypsin class of serine proteases, hemoglobins, oligosaccharide phosphorylases, nuclear receptor ligand-binding domains and retroviral proteases) confirms that experimentally many of these residues are important for allosteric communication. The agreement between the centrally conserved residues, which are key in preserving short path lengths, and residues experimentally suggested to mediate signaling further illustrates that topology plays an important role in network communication. Protein folds have evolved under constraints imposed by function. To maintain function, protein structures need to be robust to mutational events. On the other hand, robustness is accompanied by an extreme sensitivity at some crucial sites. Thus, here we propose that centrally conserved residues, whose removal increases the characteristic path length in protein networks, may relate to the system fragility. [less ▲]

Detailed reference viewed: 95 (1 UL)