Evolutionary diversification of protein–protein interactions by interface add-ons

Plach, Maximilian G.; Semmelmann, Florian; Büsch, Florian; Busch, Markus; Heizinger, Leonhard; Wysocki, Vicki H.; Merkl, Rainer; Sterner, Reinhard

doi:10.1073/pnas.1707335114

Cited by 23 publications

(20 citation statements)

References 52 publications

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“…The presence of the O-loop is thus a prerequisite for tight binding of YAP (and TAZ) and for competing effectively with VGLL. Recently, Plach et al have introduced the concept of 'interface add-ons' that are used to establish sufficient specificity and stability in protein-protein interactions [31]. Accordingly, the Oloop of YAP/TAZ could be an 'interface add-on' conferring sufficient affinity for TEAD on these two proteins in order to compete with VGLL.…”

Section: Discussionmentioning

confidence: 99%

Molecular and structural characterization of a TEAD mutation at the origin of Sveinsson's chorioretinal atrophy

et al. 2019

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Four TEAD transcription factors (TEAD1–4) mediate the signalling output of the Hippo pathway that controls organ size in humans. TEAD transcriptional activity is regulated via interactions with the YAP, TAZ and VGLL proteins. A mutation in the TEAD1 gene, Tyr421His, has been identified in patients suffering from Sveinsson's chorioretinal atrophy (SCA), an autosomal dominant eye disease. This mutation prevents the YAP/TAZ:TEAD1 interaction. In this study, we measure the affinity of YAP, TAZ and VGLL1 for the four human TEADs and find that they have a similar affinity for all TEADs. We quantitate the effect of the mutation found in SCA patients and show that it destabilizes the YAP/TAZ:TEAD interaction by about 3 kcal·mol−1. We determine the structure of YAP in complex with this mutant form of TEAD and show that the histidine residue adopts different conformations at the binding interface. The presence of this flexible residue induces the destabilization of several H‐bonds and the loss of van der Waals contacts, which explains why the Tyr421HisTEAD1 mutation has such a large destabilizing effect on the formation of the YAP:TEAD complex. Database The crystallographic data have been deposited at the RSCB Protein Data Bank (PDB, http://www.pdb.org) with the access codes: http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6HIL (wtYAP:Tyr421HisTEAD1), http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6HIK (wtYAP:Tyr429HisTEAD4)

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Section: Discussionmentioning

confidence: 99%

Molecular and structural characterization of a TEAD mutation at the origin of Sveinsson's chorioretinal atrophy

et al. 2019

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“…In two-component genetic systems, specificity of the interaction can be very tight such as for example in receptor-ligand interactions (Laub and Goulian, 2007) or bacterial toxin-antitoxin systems (Aakre et al, 2015). In these systems, the emergence of novel traits involves evolutionary modification of the interacting partners, leading to potential disruption of the interaction or to detrimental cross-talk, at least transiently (Plach et al, 2017). A central aspect of the diversification process therefore concerns the functional nature of the evolutionary intermediate.…”

Section: Introductionmentioning

confidence: 99%

Asymmetrical diversification of the receptor-ligand interaction controlling self-incompatibility in Arabidopsis

Chantreau

Poux

Lensink

et al. 2019

eLife

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How two-component genetic systems accumulate evolutionary novelty and diversify in the course of evolution is a fundamental problem in evolutionary systems biology. In the Brassicaceae, self-incompatibility (SI) is a spectacular example of a diversified allelic series in which numerous highly diverged receptor-ligand combinations are segregating in natural populations. However, the evolutionary mechanisms by which new SI specificities arise have remained elusive. Using in planta ancestral protein reconstruction, we demonstrate that two allelic variants segregating as distinct receptor-ligand combinations diverged through an asymmetrical process whereby one variant has retained the same recognition specificity as their (now extinct) putative ancestor, while the other has functionally diverged and now represents a novel specificity no longer recognized by the ancestor. Examination of the structural determinants of the shift in binding specificity suggests that qualitative rather than quantitative changes of the interaction are an important source of evolutionary novelty in this highly diversified receptor-ligand system.

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“…The simplest form of heteromeric complexes are hetero-dimers consisting of two subunits. Thus, we chose a recently compiled set of bacterial hetero-dimers with known crystal structures that do not possess additional interaction partners like DNA [16]. The corresponding PDB [17] entries were analyzed to deduce pairs of complex-forming subunits (, ) and the corresponding InterPro [18] and Pfam [19] families.…”

Section: Resultsmentioning

confidence: 99%

Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products

Esch

Merkl

2020

BMC Bioinformatics

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BackgroundThe order of genes in bacterial genomes is not random; for example, the products of genes belonging to an operon work together in the same pathway. The cotranslational assembly of protein complexes is deemed to conserve genomic neighborhoods even stronger than a common function. This is why a conserved genomic neighborhood can be utilized to predict, whether gene products form protein complexes.ResultsWe were interested to assess the performance of a neighborhood-based classifier that analyzes a large number of genomes. Thus, we determined for the genes encoding the subunits of 494 experimentally verified hetero-dimers their local genomic context. In order to generate phylogenetically comprehensive genomic neighborhoods, we utilized the tools offered by the Enzyme Function Initiative. For each subunit, a sequence similarity network was generated and the corresponding genome neighborhood network was analyzed to deduce the most frequent gene product. This was predicted as interaction partner, if its abundance exceeded a threshold, which was the frequency giving rise to the maximal Matthews correlation coefficient. For the threshold of 16%, the true positive rate was 45%, the false positive rate 0.06%, and the precision 55%. For approximately 20% of the subunits, the interaction partner was not found in a neighborhood of ± 10 genes.ConclusionsOur phylogenetically comprehensive analysis confirmed that complex formation is a strong evolutionary factor that conserves genome neighborhoods. On the other hand, for 55% of the cases analyzed here, classification failed. Either, the interaction partner was not present in a ± 10 gene window or was not the most frequent gene product.

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Evolutionary diversification of protein–protein interactions by interface add-ons

Cited by 23 publications

References 52 publications

Molecular and structural characterization of a TEAD mutation at the origin of Sveinsson's chorioretinal atrophy

Molecular and structural characterization of a TEAD mutation at the origin of Sveinsson's chorioretinal atrophy

Asymmetrical diversification of the receptor-ligand interaction controlling self-incompatibility in Arabidopsis

Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products

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