Structure of the N-terminal coiled-coil domains of the ciliary protein Rpgrip1l

Ran He; Guanhao Chen; Zhiwei Li; Jianchao Li

doi:10.1016/j.isci.2023.106249

Structure of the N-terminal coiled-coil domains of the ciliary protein Rpgrip1l

iScience. 2023 Feb 21;26(3):106249. doi: 10.1016/j.isci.2023.106249. eCollection 2023 Mar 17.

Authors

Ran He¹, Guanhao Chen¹, Zhiwei Li¹, Jianchao Li^{1

2}

Affiliations

¹ Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China.
² Department of Otorhinolaryngology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.

Abstract

Rpgrip1l is one of the key ciliary proteins located at the transition zone of the primary cilium, an important organelle for cells to sense the outer environment. Mutations in the RPGRIP1L gene are associated with various ciliopathies. Here, we focused on the N-terminal coiled-coil of Rpgrip1l. By comprehensive biochemical and structural characterizations, we demonstrated that the two predicted coiled-coil regions (CC12) located at Rpgrip1l N-terminus each can form a stable parallel dimer. We further showed that overexpression of Rpgrip1l CC12 in NIH/3T3 cells significantly shortened the length of primary cilia, and this effect depended on the dimer formation. In addition, we found that CC12 of the homolog protein Rpgrip1 in mouse and human were significantly different from Rpgrip1l. Finally, we confirmed that some disease-related mutations can alter the dimeric states of CC12 of Rpgrip1l or Rpgrip1, which might explain the pathogenic mechanisms.

Keywords: Cell biology; Molecular biology; Structural biology.