A general model for preferential hetero-oligomerization of LIN-2/7 domains: mechanism underlying directed assembly of supramolecular signaling complexes
- LIN-2/7 (L27) domains are protein interaction modules that preferentially hetero-oligomerize, a property critical for their function in directing specific assembly of supramolecular signaling complexes at synapses and other polarized cell-cell junctions. We have solved the solution structure of the heterodimer composed of the L27 domains from LIN-2 and LIN-7. Comparison of this structure with other L27 domain structures has allowed us to formulate a general model for why most L27 domains form an obligate heterodimer complex. L27 domains can be divided in two types (A and B), with each heterodimer comprising an A/B pair. We have identified two keystone positions that play a central role in discrimination. The residues at these positions are energetically acceptable in the context of an A/B heterodimer, but would lead to packing defects or electrostatic repulsion in the context of A/A and B/B homodimers. As predicted by the model, mutations of keystone residues stabilize normally strongly disfavored homodimers. Thus, L27 domains are specifically optimized to avoid homodimeric interactions.
Verfasserangaben: | Keiko Y. Petrosky, Horng D. Ou, Frank LöhrORCiD, Volker DötschORCiDGND, Wendell LimORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-759103 |
DOI: | https://doi.org/10.1074/jbc.M506536200 |
ISSN: | 0021-9258 |
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/16147993 |
Titel des übergeordneten Werkes (Englisch): | Journal of biological chemistry |
Verlag: | American Society for Biochemistry and Molecular Biology Publications |
Verlagsort: | Bethesda, Md |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 04.01.2021 |
Jahr der Erstveröffentlichung: | 2005 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 07.03.2024 |
Jahrgang: | 280.2005 |
Ausgabe / Heft: | 46 |
Seitenzahl: | 9 |
Erste Seite: | 38528 |
Letzte Seite: | 38536 |
Institute: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | ![]() |