Connecting the αα-hubs: same fold, disordered ligands, new functions
Publikation: Bidrag til tidsskrift › Letter › Forskning › fagfællebedømt
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Connecting the αα-hubs : same fold, disordered ligands, new functions. / Staby, Lasse; Bugge, Katrine; Falbe-Hansen, Rasmus Greve; Salladini, Edoardo; Skriver, Karen; Kragelund, Birthe B.
I: Cell Communication and Signaling, Bind 19, 2, 2021.Publikation: Bidrag til tidsskrift › Letter › Forskning › fagfællebedømt
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TY - JOUR
T1 - Connecting the αα-hubs
T2 - same fold, disordered ligands, new functions
AU - Staby, Lasse
AU - Bugge, Katrine
AU - Falbe-Hansen, Rasmus Greve
AU - Salladini, Edoardo
AU - Skriver, Karen
AU - Kragelund, Birthe B.
PY - 2021
Y1 - 2021
N2 - Background: Signal fidelity depends on protein-protein interaction-'hubs' integrating cues from large interactomes. Recently, and based on a common secondary structure motif, the alpha alpha-hubs were defined, which are small alpha-helical domains of large, modular proteins binding intrinsically disordered transcriptional regulators.Methods: Comparative structural biology.Results: We assign the harmonin-homology-domain (HHD, also named the harmonin N-terminal domain, NTD) present in large proteins such as harmonin, whirlin, cerebral cavernous malformation 2, and regulator of telomere elongation 1 to the alpha alpha-hubs. The new member of the alpha alpha-hubs expands functionality to include scaffolding of supra-modular complexes mediating sensory perception, neurovascular integrity and telomere regulation, and reveal novel features of the alpha alpha-hubs. As a common trait, the alpha alpha-hubs bind intrinsically disordered ligands of similar properties integrating similar cellular cues, but without cross-talk.Conclusion: The inclusion of the HHD in the alpha alpha-hubs has uncovered new features, exemplifying the utility of identifying groups of hub domains, whereby discoveries in one member may cross-fertilize discoveries in others. These features make the alpha alpha-hubs unique models for decomposing signal specificity and fidelity. Using these as models, together with other suitable hub domain, we may advance the functional understanding of hub proteins and their role in cellular communication and signaling, as well as the role of intrinsically disordered proteins in signaling networks.
AB - Background: Signal fidelity depends on protein-protein interaction-'hubs' integrating cues from large interactomes. Recently, and based on a common secondary structure motif, the alpha alpha-hubs were defined, which are small alpha-helical domains of large, modular proteins binding intrinsically disordered transcriptional regulators.Methods: Comparative structural biology.Results: We assign the harmonin-homology-domain (HHD, also named the harmonin N-terminal domain, NTD) present in large proteins such as harmonin, whirlin, cerebral cavernous malformation 2, and regulator of telomere elongation 1 to the alpha alpha-hubs. The new member of the alpha alpha-hubs expands functionality to include scaffolding of supra-modular complexes mediating sensory perception, neurovascular integrity and telomere regulation, and reveal novel features of the alpha alpha-hubs. As a common trait, the alpha alpha-hubs bind intrinsically disordered ligands of similar properties integrating similar cellular cues, but without cross-talk.Conclusion: The inclusion of the HHD in the alpha alpha-hubs has uncovered new features, exemplifying the utility of identifying groups of hub domains, whereby discoveries in one member may cross-fertilize discoveries in others. These features make the alpha alpha-hubs unique models for decomposing signal specificity and fidelity. Using these as models, together with other suitable hub domain, we may advance the functional understanding of hub proteins and their role in cellular communication and signaling, as well as the role of intrinsically disordered proteins in signaling networks.
KW - Interactome
KW - Intrinsically disordered protein
KW - IDP
KW - NCBD
KW - PAH
KW - RST
KW - HHD
KW - Signaling
KW - TAFH
KW - Hub proteins
KW - INTRINSIC DISORDER
KW - SIN3 COREPRESSOR
KW - PROTEIN
KW - COMPLEX
KW - BINDING
KW - REVEALS
KW - DOMAIN
KW - PAH1
U2 - 10.1186/s12964-020-00686-8
DO - 10.1186/s12964-020-00686-8
M3 - Letter
C2 - 33407551
VL - 19
JO - Cell Communication and Signaling
JF - Cell Communication and Signaling
SN - 1478-811X
M1 - 2
ER -
ID: 255503262