| RRC ID |
44927
|
| 著者 |
Nakamura Y, Hasebe A, Takahashi K, Iijima M, Yoshimoto N, Maturana AD, Ting K, Kuroda S, Niimi T.
|
| タイトル |
Oligomerization-induced conformational change in the C-terminal region of Nel-like molecule 1 (NELL1) protein is necessary for the efficient mediation of murine MC3T3-E1 cell adhesion and spreading.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
NELL1 is a large oligomeric secretory glycoprotein that functions as an osteoinductive factor. NELL1 contains several conserved domains, has structural similarities to thrombospondin 1, and supports osteoblastic cell adhesion through integrins. To define the structural requirements for NELL1-mediated cell adhesion, we prepared a series of recombinant NELL1 proteins (intact, deleted, and cysteine-mutant) from a mammalian expression system and tested their activities. A deletion analysis demonstrated that the C-terminal cysteine-rich region of NELL1 is critical for the cell adhesion activity of NELL1. Reducing agent treatment decreased the cell adhesion activity of full-length NELL1 but not of its C-terminal fragments, suggesting that the intramolecular disulfide bonds within this region are not functionally necessary but that other disulfide linkages in the N-terminal region of NELL1 may be involved in cell adhesion activity. By replacing cysteine residues with serines around the coiled-coil domain of NELL1, which is responsible for oligomerization, we created a mutant NELL1 protein that was unable to form homo-oligomers, and this monomeric mutant showed substantially lower cell adhesion activity than intact NELL1. These results suggest that an oligomerization-induced conformational change in the C-terminal region of NELL1 is important for the efficient mediation of cell adhesion and spreading by NELL1.
|
| 巻・号 |
289(14)
|
| ページ |
9781-94
|
| 公開日 |
2014-4-4
|
| DOI |
10.1074/jbc.M113.507020
|
| PII |
S0021-9258(20)42044-7
|
| PMID |
24563467
|
| PMC |
PMC3975024
|
| MeSH |
Animals
Calcium-Binding Proteins / genetics
Calcium-Binding Proteins / metabolism*
Cell Adhesion / physiology
Cell Line
Cell Movement / physiology*
Glycoproteins / genetics
Glycoproteins / metabolism*
Mice
Mutation
Protein Multimerization / physiology*
Protein Structure, Quaternary
Protein Structure, Tertiary
|
| IF |
4.238
|
| 引用数 |
10
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
