# 1H, 13C, and 15N resonance assignment of the C terminal region of the disordered postsynaptic scaffold protein GKAP

## TL;DR

This study identifies the structure and function of the disordered C-terminal region of the GKAP protein, revealing its potential role in binding to Shank proteins.

## Contribution

The study provides resonance assignments and structural insights into the disordered C-terminal region of GKAP, revealing its helical propensity and binding capability.

## Key findings

- The C-terminal 43 residues of GKAP have micromolar binding affinity to Shank1 PDZ.
- Chemical shifts indicate the region is disordered but has helical propensity in two areas.
- The structure resembles C-termini of E6 and RSK1 proteins, suggesting functional relevance.

## Abstract

Guanylate kinase-associated protein, GKAP, is a largely disordered scaffold protein with multiple interaction partners, playing a role in the organization of the postsynaptic protein network. Its C-terminus contains a binding motif for the PDZ domain of Shank proteins, another class of postsynaptic scaffolds. Based on predictions, this motif is preceded by a ~ 40-residue disordered segment with no known additional binding sites or established functional role. Here we report the expression, purification, and 1H, 13C and 15N resonance assignment of the GKAP Ct43 construct containing the C-terminal 43 residues. This region is functionally intact, having a binding affinity to Shank1 PDZ in the micromolar range. Chemical shifts indicate that this region is indeed disordered but displays helical propensity in two regions. The short, slightly helical segment immediately before a PDZ-binding motif is somewhat comparable to the structural organization observed at the C-terminus of the E6 and RSK1 proteins, but its significance in GKAP is yet to be explored.

The online version contains supplementary material available at 10.1007/s12104-025-10253-2.