Limits...
ECOD: an evolutionary classification of protein domains.

Cheng H, Schaeffer RD, Liao Y, Kinch LN, Pei J, Shi S, Kim BH, Grishin NV - PLoS Comput. Biol. (2014)

Bottom Line: The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates.This synchronization with PDB uniquely distinguishes ECOD among all protein classifications.Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

ABSTRACT
Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

Show MeSH
Hierarchical levels of ECOD.Domains placed within the same Architecture share similar secondary structure content (helix, cyan; sheet, yellow) and geometric arrangement. Domains placed within the same X-group share similar structure but lack a convincing argument for homology (vs. analogy), while those placed within the same H-groups are homologous. X- and H- group structures are colored in rainbow by consecutive secondary structure elements. T-groups distinguish homologous domains with notable differences in topology, such as the illustrated Rift-related metafold [18]. Rift-related half-barrels (colored blue and red) are consistent among the domains, but permutations and strand swaps (green) modify the topology.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4256011&req=5

pcbi-1003926-g002: Hierarchical levels of ECOD.Domains placed within the same Architecture share similar secondary structure content (helix, cyan; sheet, yellow) and geometric arrangement. Domains placed within the same X-group share similar structure but lack a convincing argument for homology (vs. analogy), while those placed within the same H-groups are homologous. X- and H- group structures are colored in rainbow by consecutive secondary structure elements. T-groups distinguish homologous domains with notable differences in topology, such as the illustrated Rift-related metafold [18]. Rift-related half-barrels (colored blue and red) are consistent among the domains, but permutations and strand swaps (green) modify the topology.

Mentions: ECOD is a hierarchical classification with five main levels (Fig. 2, from top to bottom): architecture (A), possible homology (X), homology (H), topology (T), and family (F). The architecture level (A) groups domains with similar secondary structure compositions and geometric shapes. The possible homology level (X) groups domains where some evidence exists to demonstrate homology (but where further evidence is needed). The homology level (H) groups together domains with common ancestry as suggested by high sequence-structure scores, functional similarity, shared unusual features [25], and literature. The topology level (T) groups domains with similar topological connections. The family level (F) groups domains with significant sequence similarity (primarily according to Pfam, secondarily by HHsearch-based clustering).


ECOD: an evolutionary classification of protein domains.

Cheng H, Schaeffer RD, Liao Y, Kinch LN, Pei J, Shi S, Kim BH, Grishin NV - PLoS Comput. Biol. (2014)

Hierarchical levels of ECOD.Domains placed within the same Architecture share similar secondary structure content (helix, cyan; sheet, yellow) and geometric arrangement. Domains placed within the same X-group share similar structure but lack a convincing argument for homology (vs. analogy), while those placed within the same H-groups are homologous. X- and H- group structures are colored in rainbow by consecutive secondary structure elements. T-groups distinguish homologous domains with notable differences in topology, such as the illustrated Rift-related metafold [18]. Rift-related half-barrels (colored blue and red) are consistent among the domains, but permutations and strand swaps (green) modify the topology.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256011&req=5

pcbi-1003926-g002: Hierarchical levels of ECOD.Domains placed within the same Architecture share similar secondary structure content (helix, cyan; sheet, yellow) and geometric arrangement. Domains placed within the same X-group share similar structure but lack a convincing argument for homology (vs. analogy), while those placed within the same H-groups are homologous. X- and H- group structures are colored in rainbow by consecutive secondary structure elements. T-groups distinguish homologous domains with notable differences in topology, such as the illustrated Rift-related metafold [18]. Rift-related half-barrels (colored blue and red) are consistent among the domains, but permutations and strand swaps (green) modify the topology.
Mentions: ECOD is a hierarchical classification with five main levels (Fig. 2, from top to bottom): architecture (A), possible homology (X), homology (H), topology (T), and family (F). The architecture level (A) groups domains with similar secondary structure compositions and geometric shapes. The possible homology level (X) groups domains where some evidence exists to demonstrate homology (but where further evidence is needed). The homology level (H) groups together domains with common ancestry as suggested by high sequence-structure scores, functional similarity, shared unusual features [25], and literature. The topology level (T) groups domains with similar topological connections. The family level (F) groups domains with significant sequence similarity (primarily according to Pfam, secondarily by HHsearch-based clustering).

Bottom Line: The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates.This synchronization with PDB uniquely distinguishes ECOD among all protein classifications.Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

ABSTRACT
Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

Show MeSH