The KN domain of KANK proteins contains separable talin-binding and intramolecular interaction modules
- 1University of Liverpool
Abstract
KANK proteins link integrin adhesions to the cortical microtubule stabilising complex (CMSC) through interactions with the adhesion adaptor talin. However, how KANK proteins are regulated remains unclear. Here we show that the KN domain of KANK proteins contains separable regions that mediate talin binding and a conserved intramolecular interaction. Using fluorescence polarisation, NMR spectroscopy and structural analysis, we map an interaction between the N-terminal KN domain and the C-terminal ankyrin repeat domain and identify residues 60-68 of the KN domain as required for this intramolecular interaction. In contrast, the canonical LD motif within residues 30-60 mediates binding to talin. Deletion of residues 60-68 disrupts the intramolecular interaction while preserving talin binding, demonstrating that the KN domain contains distinct modules for talin engagement and intramolecular regulation. This regulatory architecture is conserved across the KANK family, although sequence variation modulates the strength of the intramolecular interaction. Together, these findings identify a modular organisation within the KANK KN domain that separates talin recognition from intramolecular regulation and is consistent with an autoinhibitory mechanism.
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BibTeX
@misc{khan2026domain,
title = {{The KN domain of KANK proteins contains separable talin-binding and intramolecular interaction modules}},
author = {R. B. Khan and T. Kallem and A. K. Singh and B. T. Goult},
howpublished = {bioRxiv},
year = {2026},
month = jun,
doi = {10.64898/2026.06.09.731086},
url = {https://www.biorxiv.org/content/10.64898/2026.06.09.731086v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - The KN domain of KANK proteins contains separable talin-binding and intramolecular interaction modules
AU - R. B. Khan
AU - T. Kallem
AU - A. K. Singh
AU - B. T. Goult
PY - 2026
DA - 2026/06/09
PB - bioRxiv
DO - 10.64898/2026.06.09.731086
UR - https://www.biorxiv.org/content/10.64898/2026.06.09.731086v2
AB - KANK proteins link integrin adhesions to the cortical microtubule stabilising complex (CMSC) through interactions with the adhesion adaptor talin. However, how KANK proteins are regulated remains unclear. Here we show that the KN domain of KANK proteins contains separable regions that mediate talin binding and a conserved intramolecular interaction. Using fluorescence polarisation, NMR spectroscopy and structural analysis, we map an interaction between the N-terminal KN domain and the C-terminal ankyrin repeat domain and identify residues 60-68 of the KN domain as required for this intramolecular interaction. In contrast, the canonical LD motif within residues 30-60 mediates binding to talin. Deletion of residues 60-68 disrupts the intramolecular interaction while preserving talin binding, demonstrating that the KN domain contains distinct modules for talin engagement and intramolecular regulation. This regulatory architecture is conserved across the KANK family, although sequence variation modulates the strength of the intramolecular interaction. Together, these findings identify a modular organisation within the KANK KN domain that separates talin recognition from intramolecular regulation and is consistent with an autoinhibitory mechanism.
ER -