Residual flexibility in the topologically constrained multivalent complex between the GKAP scaffold and LC 8 hub proteins

Guanylate kinase‐associated protein (GKAP) is a large postsynaptic scaffold protein bearing two closely spaced noncanonical binding sites for the bivalent dynein light chain LC8 hub protein. This might allow the formation of heterogeneous complexes with different sizes and topologies. Here, we show...

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Bibliographic Details
Main Authors: Nagy-Kanta Eszter
Kálmán Zsófia Etelka
Tossavainen Helena
Juhász Tünde
Farkas Fanni
Hegedüs József
Keresztes Melinda
Beke‐Somfai Tamás
Gáspári Zoltán
Permi Perttu
Péterfia Bálint
Format: Article
Published: 2025
Series:FEBS JOURNAL - No. -
Subjects:
doi:10.1111/febs.70219

mtmt:36303973
Online Access:https://publikacio.ppke.hu/2753

MARC

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520 3 |a Guanylate kinase‐associated protein (GKAP) is a large postsynaptic scaffold protein bearing two closely spaced noncanonical binding sites for the bivalent dynein light chain LC8 hub protein. This might allow the formation of heterogeneous complexes with different sizes and topologies. Here, we show that a well‐defined hexameric complex is formed, composed of two GKAP molecules and two LC8 dimers. Using nuclear magnetic resonance (NMR) spectroscopy, we demonstrate that the LC8‐binding segment of GKAP is intrinsically disordered and the flexibility of the linker region is largely retained even in the complex form. Molecular dynamics calculations suggest that, besides the tightly bound residues, the hexamer also exhibits several dynamically interchanging interactions, and that the two LC8 dimers might interact with each other. The flanking regions of the two binding sites on GKAP exhibit different interaction patterns, hinting at additional contacts that might explain the fixed stoichiometry of the assembly. Our results demonstrate that constrained stoichiometry can coexist with substantial flexibility in a multivalent system. 
650 4 |a Biokémia és molekuláris biológia 
700 0 1 |a Kálmán Zsófia Etelka  |e aut 
700 0 1 |a Tossavainen Helena  |e aut 
700 0 1 |a Juhász Tünde  |e aut 
700 0 1 |a Farkas Fanni  |e aut 
700 0 1 |a Hegedüs József  |e aut 
700 0 1 |a Keresztes Melinda  |e aut 
700 0 1 |a Beke‐Somfai Tamás  |e aut 
700 0 1 |a Gáspári Zoltán  |e aut 
700 0 1 |a Permi Perttu  |e aut 
700 0 1 |a Péterfia Bálint  |e aut 
856 4 0 |u https://publikacio.ppke.hu/id/eprint/2753/1/TheFEBSJournal-2025-NagyKanta-Residualflexibilityinthetopologicallyconstrainedmultivalentcomplexbetween.pdf  |z Dokumentum-elérés