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. 2022 Jul 5;50(W1):W210-W215.
doi: 10.1093/nar/gkac387.

Dali server: structural unification of protein families

Liisa Holm  1
Affiliations

Dali server: structural unification of protein families

Liisa Holm. Nucleic Acids Res. .

Abstract

Protein structure is key to understanding biological function. Structure comparison deciphers deep phylogenies, providing insight into functional conservation and functional shifts during evolution. Until recently, structural coverage of the protein universe was limited by the cost and labour involved in experimental structure determination. Recent breakthroughs in deep learning revolutionized structural bioinformatics by providing accurate structural models of numerous protein families for which no structural information existed. The Dali server for 3D protein structure comparison is widely used by crystallographers to relate new structures to pre-existing ones. Here, we report two most recent upgrades to the web server: (i) the foldomes of key organisms in the AlphaFold Database (version 1) are searchable by Dali, (ii) structural alignments are annotated with protein families. Using these new features, we discovered a novel functionally diverse subgroup within the WRKY/GCM1 clan. This was accomplished by linking the structurally characterized SWI/SNF and NAM families as well as the structural models of the CG-1 family and uncharacterized proteins to the structure of Gti1/Pac2, a previously known member of the WRKY/GCM1 clan. The Dali server is available at http://ekhidna2.biocenter.helsinki.fi/dali. This website is free and open to all users and there is no login requirement.

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Figures

Graphical Abstract
Graphical Abstract
Dali server supports structural searches against the Protein Data Bank and AlphaFold Database and annotates structural alignments with Pfam graphics.
Figure 1.
Figure 1.
Left: Residue-wise proteome coverage by AlphaFold. Residues with pLDDT above 70 are confidently modelled. Species identified by Swissprot short names, sorted by fraction of confidently modelled residues. Right: AlphaFold Database model of Ssr4 superimposed onto the crystal structure of the N-terminal domain (7k7v, cyan). The AF-DB model is colored by pLDDT (red: high values, blue: low values). The crystal structure has an N-terminal His tag not present in the natural protein. The structures superimpose with 0.2 Å rmsd over 180 CA atoms. Image rendered by Pymol using superimposed coordinates downloaded from the Dali web server.
Figure 2.
Figure 2.
Left: Meaning of visual cues in stacked Pfam graphics. Placeholder gaps are introduced in order to show structurally equivalent blocks (dark hue) aligned vertically throughout the stack. Unaligned segments (tall bars) are tucked beneath each other to save space. Right: Stacked Pfam graphics of structural neighbors. Pfam annotations are shown when you hover the cursor above a green cartouche. Here, structural alignment unifies the four N-terminal domain families.
Figure 3.
Figure 3.
Top, left to right: Superimposed structures of 4m8bR (Gti1/Pac2 family) complexed with dsDNA, 7k7vA (22) (residues 1–151) with transplanted dsDNA, CG-1 model (residues 14–139 of ahoyA) with transplanted dsDNA, abinA model (residues 1–133) with transplanted dsDNA. The recognition loop is at the center of the image (yellow highlight). Images rendered by Pymol using superimposed coordinates downloaded from the Dali web server. Bottom: Stacked structural alignment anchored on ahoyA N-terminal domain (adapted from web server output). Structurally unaligned insertions relative to ahoyA are omitted. Helices are green, beta strands are blue. The red DxxxW motif stabilizes the recognition loop in 4m8bR (24).
See this image and copyright information in PMC

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