Structural Interplays in the Flexible N-Terminus and Scaffolding Domain of Human Membrane Protein Caveolin 3

Membranes

Min-Duk Seo¹  Jinhwa Jang²  Sung-Hee Lee²  Ji-Hun Kim²  Hae-Jun Park²  Hyung-Sik Won³  Jinhyuk Lee⁴  Kyung-Suk Ryu⁵  Eun-Hee Kim⁵ 

[1] College of Pharmacy and Department of Molecular Science and Technology, Ajou University, Suwon, Gyeonggi 16499, Korea;College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Korea;Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju, Chungbuk 27478, Korea;Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea;Research Center for Bioconvergence Analysis, Korea Basic Science Institute, 162 Yeongudanji-Ro, Ochang-Eup, Cheongju, Chungbuk 28119, Korea;

关键词: caveolin 3;    nuclear magnetic resonance;    paramagnetic relaxation enhancement;    signature motif;    oligomerization;   

DOI  :  10.3390/membranes11020082

来源: DOAJ

【 摘 要 】

Caveolins are critical for the formation of caveolae, which are small invaginations of the plasma membrane involved in a variety of biological processes. Caveolin 3 (Cav3), one of three caveolin isoforms, is an integral membrane protein mainly expressed in muscle tissues. Although various human diseases associated with Cav3 have been reported, structural characterization of Cav3 in the membrane has not been investigated in enough depth to understand the structure–function relationship. Here, using solution NMR, we characterized membrane association, structural communications, and molecular dynamics of the monomeric Cav3 in detergent micelle environment, particularly focused on the whole N-terminal part that is composed of the flexible N-terminus and the scaffolding domain. The results revealed a complicated structural interplay of the individual segments composing the whole N-terminal part, including the pH-dependent helical region, signature motif-like region, signature motif, and scaffolding domain. Collectively, the present study provides novel structural insights into the whole N-terminal part of Cav3 that plays important biological roles in cellular processes and diseases. In particular, given that several disease-related mutations are located at the whole N-terminal part of Cav3, the sophisticated communications in the whole N-terminal segments are likely to have relevance to the molecular basis of Cav3-related disease.

【 授权许可】

Unknown