Journal Article

FZJ-2026-05823

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural and functional insights into the p160 Rho-associated coiled-coil-containing protein kinase ROCK

Dubey, B. N. (Corresponding author) ; Rezaei Adariani, S. ; Gremer, L.FZJ* ; Dvorsky, R. ; Nie, Y. ; Amin, E. ; Moll, J. M. ; Zhang, S. ; Smits, S. H. J. ; Graewert, M. A. ; Willbold, D. ; Groth, G. ; Nagel, L. ; Pospich, S. ; Ahmadian, M. R. (Corresponding author)

2026
Macmillan Publishers Limited, part of Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s42004-026-02258-2  doi:10.34734/FZJ-2026-05823

Abstract: Rho-associated protein kinases (ROCK1/2) are critical regulators of fundamental cellular processes and represent promising therapeutic targets for various pathologies, particularly cardiovascular disease. While the terminal globular kinase domain and the PH-C1 tandem (PHn-C1-PHc) are well characterized, the sequence-structure-function relationship of the central amphipathic α-helical segment remains poorly understood. Utilizing an integrative biophysical approach—including multiangle light scattering (MALS), analytical ultracentrifugation (AUC), small-angle X-ray scattering (SAXS), negative-stain electron microscopy (EM), X-ray crystallography, and 3D molecular modeling—we elucidate the structural organization of the central coiled-coil region of ROCK1. Notably, the 2.2 Å resolution crystal structure of the homology region 1 (HR1) of ROCK1 reveals a canonical parallel coiled-coil dimer. This structural arrangement diverges significantly from the antiparallel coiled-coil HR1 module found in other Rho effector kinases. Combined with the structural reconstitution of fulllength ROCK1, our data demonstrates that the central segment of ROCK1 forms a highly elongated coiled-coil dimer. Furthermore, EM analysis of the isolated full coiled-coil domain uncovers a dynamic oligomerization state, transitioning between a dimer and a tetramer. Together, these biophysical insights establish a foundation that opens avenues for future investigation into ROCK1 regulation, activation, and downstream signaling mechanisms.

---

Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2026

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---