Protodomains: Symmetry-Related Supersecondary Structures in Proteins and Self-Complementarity

Youkharibache, Philippe

doi:10.1007/978-1-4939-9161-7_10

Cited by 9 publications

(42 citation statements)

References 87 publications

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“…The diversity and complexity of GPCRs is such that it is extremely difficult to infer co-evolution patterns between protodomains through a simple observation of a sequence alignment. While the D 2.50 /F 6.44 xxxW 6.48 pattern is relatively easy to pick (see earlier discussion), there are certainly other co-evolved pairs (or larger sets of residues) in GPCRs to detect, as we usually find in pseudo-symmetric domains (Youkharibache 2019). Another pair of residues/motifs that are related in function are the symmetrically related pair in TM3 and TM7: S 3.39 /N 7.45 S 7.46 .…”

Section: Each Pseudo-symmetric Protein Shows a Unique Protodomain Co-mentioning

confidence: 89%

“…Symmetry in quaternary structures is pervasive and has been widely studied (Goodsell and Olson 2000;Levy et al 2006;Rose et al 2015), as compared to symmetry in tertiary structures. The latter could in fact be described as a pseudo-quaternary organization of protodomains (Myers-Turnbull et al 2014;Youkharibache 2019). A recent biophysical study on the ClC chloride transporter found that the transporter is made up of two halves that fold independently as stable subunits, suggesting an evolutionary history of a stable protodomain that duplicated (Min et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins

2020

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The polytopic helical membrane proteome is dominated by proteins containing seven transmembrane helices (7TMHs). They cannot be grouped under a monolithic fold or superfold. However, a parallel structural analysis of folds around that magic number of seven in distinct protein superfamilies (SWEET, PnuC, TRIC, FocA, Aquaporin, GPCRs) reveals a common homology, not in their structural fold, but in their systematic pseudo-symmetric construction during their evolution. Our analysis leads to guiding principles of intragenic duplication and pseudo-symmetric assembly of ancestral transmembrane helical protodomains, consisting of 3 (or 4) helices. A parallel deconstruction and reconstruction of these domains provides a structural and mechanistic framework for their evolutionary paths. It highlights the conformational plasticity inherent to fold formation itself, the role of structural as well as functional constraints in shaping that fold, and the usefulness of protodomains as a tool to probe convergent vs divergent evolution. In the case of FocA vs. Aquaporin, this protodomain analysis sheds new light on their potential divergent evolution at the protodomain level followed by duplication and parallel evolution of the two folds. GPCR domains, whose function does not seem to require symmetry, nevertheless exhibit structural pseudosymmetry. Their construction follows the same protodomain assembly as any other pseudo-symmetric protein suggesting their potential evolutionary origins. Interestingly, all the 6/7/8TMH pseudo-symmetric folds in this study also assemble as oligomeric forms in the membrane, emphasizing the role of symmetry in evolution, revealing self-assembly and co-evolution not only at the protodomain level but also at the domain level.

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Section: Each Pseudo-symmetric Protein Shows a Unique Protodomain Co-mentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins

2020

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“…A pseudo symmetric domain is formed of two or more protodomains, according to an accepted duplication-fusion mechanism (Lee and Blaber 2011), and multiple examples of highly diversified structural folds have been known for a long time (Youkharibache 2019). Structurally, it is important to realize that the knowledge of protodomains and symmetry operators define a pseudo-symmetric protein domain entirely, apart from a variable linker region, most often short, chaining protodomains within a domain (Youkharibache 2019). Interestingly, a pseudo-symmetric domain is a tertiary structure that can also be considered a pseudo-quaternary structure, and can be analyzed according to symmetry groups (C2 or higher C3, C4 … D2, ...Dn), with a C2 symmetry prevalence in the known structural protein universe (PDB symmetry statistics).…”

Section: Pseudo Symmetry and Ancient Evolution Of The Ig Foldmentioning

confidence: 99%

“…Interestingly, a pseudo-symmetric domain is a tertiary structure that can also be considered a pseudo-quaternary structure, and can be analyzed according to symmetry groups (C2 or higher C3, C4 … D2, ...Dn), with a C2 symmetry prevalence in the known structural protein universe (PDB symmetry statistics). The symmetric assembly of (chained) protodomains is a general property found in biopolymers beyond proteins, as in RNA riboswitches for example (Youkharibache 2019;Jones and Ferré-D'Amaré 2015), demonstrating a general duplication mechanism in biopolymers with symmetric self assembly of the duplicated parts, beyond the realm of proteins, and already present in the RNA world when considering the ribosomal peptidyl transferase center (PTC) (Bashan et al 2003) as a remnant of an ancient proto-ribosome.…”

Section: Pseudo Symmetry and Ancient Evolution Of The Ig Foldmentioning

confidence: 99%

“…20% of known protein folds/domains are pseudo-symmetric (Myers-Turnbull et al 2014) and that in each structural class (Lo Conte et al 2000) the most diversified fold exhibits pseudo symmetry, suggesting a link between symmetry and evolution. In particular, two classes of folds show a higher proportion of pseudo-symmetric domains: membrane proteins, with for example GPCRs (Youkharibache, Tran, and Abrol 2020), and beta folds, with chief among them the Ig-fold (Youkharibache 2019). The Ig-fold is present in over 2% of human genes in the human genome (Lander et al 2001) and it is overly represented in the surfaceome/immunome (Bausch-Fluck, Milani, and Wollscheid 2019;Díaz-Ramos, Engel, and Bastos 2011).…”

Section: Introduction Tertiary Pseudo Symmetry Of the Ig Foldmentioning

confidence: 99%

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Topological and Structural Plasticity of the single Ig fold and the double Ig fold present in CD19

Youkharibache

2021

Preprint

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The Ig-fold has had a remarkable success in vertebrate evolution, with a presence in over 2% of human genes. The Ig-fold is not just the elementary structural domain of antibodies and TCRs, it is also at the heart of a staggering 30% of immunologic cell surface receptors, making it a major orchestrator of cell-cell-interactions. While BCRs, TCRs, and numerous Ig-based cell surface receptors form homo or heterodimers on the same cell surface (in cis), many of them interface as ligand-receptors (checkpoints) on interacting cells (in trans) through their Ig domains. New Ig-Ig interfaces are still being discovered between Ig-based cell surface receptors, even in well known families such as B7. What is largely ignored however is that the Ig-fold itself is pseudo-symmetric, a property that makes the Ig-domain a versatile self-associative 3D structure and may in part explain its success in evolution, especially through its ability to bind in cis or in trans in the context of cell surface receptor-ligand interactions. In this paper we review the Ig domains tertiary and quaternary pseudo symmetries, with a particular attention to the newly identified double Ig fold in the solved CD19 molecular structure to highlight the underlying fundamental folding elements of Ig domains, i.e. Ig protodomains. This pseudosymmetric property of Ig domains gives us a decoding frame of reference to understand the fold, relate all Ig-domain forms, single or double, and suggest new protein engineering avenues.

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Substrate selectivity and unique sequence signatures in SWEET/semiSWEET homologs of four taxonomic groups: Sequence analysis and phylogenetic studies

Gupta,

Sankararamakrishnan

2024

Proteins

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The recently discovered SWEET (Sugar Will Eventually be Exported Transporter) proteins are involved in the selective transport of monosaccharides and disaccharides. The prokaryotic counterparts, semiSWEETs, form dimers with each monomer forming a triple‐helix transmembrane bundle (THB). The longer eukaryotic SWEETs have seven transmembrane helices with two THBs and a linker helix. Structures of semiSWEETs/SWEETs have been determined experimentally. Experimental studies revealed the role of plant SWEETs in vital physiological processes and identified residues responsible for substrate selectivity. However, SWEETs/semiSWEETs from metazoans and bacteria are not characterized. In this study, we used structure‐based sequence alignment and compared more than 2000 SWEET/semiSWEETs from four different taxonomic groups. Conservation of residue/chemical property was examined at all positions. Properties of clades/subclades of phylogenetic trees from each taxonomic group were analyzed. Conservation pattern of known residues in the selectivity‐filter was used to predict the substrate preference of plant SWEETs and some clusters of metazoans and bacteria. Some residues at the gating and substrate‐binding regions, pore‐facing positions and at the helix–helix interface are conserved across all taxonomic groups. Conservation of polar/charged residues at specific pore‐facing positions, helix–helix interface and in loops seems to be unique for plant SWEETs. Overall, the number of conserved residues is less in metazoan SWEETs. Plant and metazoan SWEETs exhibit high conservation of four and three proline residues respectively in “proline tetrad.” Further experimental studies can validate the predicted substrate selectivity and significance of conserved polar/charged/aromatic residues at structurally and functionally important positions of SWEETs/semiSWEETs in plants, metazoans and bacteria.

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Protodomains: Symmetry-Related Supersecondary Structures in Proteins and Self-Complementarity

Cited by 9 publications

References 87 publications

Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins

Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins

Topological and Structural Plasticity of the single Ig fold and the double Ig fold present in CD19

Substrate selectivity and unique sequence signatures in SWEET/semiSWEET homologs of four taxonomic groups: Sequence analysis and phylogenetic studies

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