TY  - JOUR
A1  - Petrosky, Keiko Y.
A1  - Ou, Horng D.
A1  - Löhr, Frank
A1  - Dötsch, Volker
A1  - Lim, Wendell
T1  - A general model for preferential hetero-oligomerization of LIN-2/7 domains: mechanism underlying directed assembly of supramolecular signaling complexes
T2  - Journal of biological chemistry
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75910
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-759103
SN  - 0021-9258
VL  - 280.2005
IS  - 46
SP  - 38528
EP  - 38536
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -