Related Experiment Videos
The crystal structure of human MRP14 (S100A9), a Ca(2+)-dependent regulator protein in inflammatory process
Hiroshi Itou1, Min Yao, Ikuko Fujita
1Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
Abstract:
Human MRP14 (hMRP14) is a Ca(2+)-binding protein from the S100 family of proteins. This protein is co-expressed with human MRP8 (hMRP8), a homologue protein in myeloid cells, and plays an indispensable role in Ca(2+)-dependent functions during inflammation. This role includes the activation of Mac-1, the beta(2) integrin which is involved in neutrophil adhesion to endothelial cells. The crystal structure of the holo form of hMRP14 was analyzed at 2.1 A resolution. hMRP14 is distinguished from other S100 member proteins by its long C-terminal region, and its structure shows that the region is extensively flexible. In this crystal structure of hMRP14, Chaps molecules bind to the hinge region that connects two EF-hand motifs, which suggests that this region is a target-binding site of this protein. Based on a structural comparison of hMRP14 with hMRP8 and human S100A12 (hS100A12) that is another homologue protein, the character of MRP8/14 hetero-complex and the functional significance of the flexibility of the C-terminal region of hMRP14 are discussed.
Insights
Human MRP14 (hMRP14), a calcium-binding protein, is crucial for myeloid cell functions during inflammation. Its crystal structure reveals a flexible C-terminal region and a potential target-binding site, offering insights into neutrophil adhesion.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Human MRP14 (hMRP14) is a Ca(2+)-binding protein belonging to the S100 family.
- It is co-expressed with human MRP8 (hMRP8) in myeloid cells and is vital for Ca(2+)-dependent inflammatory functions.
- hMRP14, along with hMRP8, activates Mac-1, a beta(2) integrin essential for neutrophil adhesion to endothelial cells.
Purpose of the Study:
- To determine the crystal structure of the holo form of human MRP14 (hMRP14).
- To investigate the binding interactions and structural characteristics of hMRP14.
- To compare the structure of hMRP14 with homologous proteins (hMRP8, hS100A12) and discuss the functional implications.
Main Methods:
- X-ray crystallography was used to analyze the crystal structure of hMRP14 at 2.1 Å resolution.
- Structural comparisons were made between hMRP14, hMRP8, and human S100A12.
- Analysis of the binding of Chaps molecules to the hinge region of hMRP14.
Main Results:
- The crystal structure of holo hMRP14 was determined at 2.1 Å resolution.
- hMRP14 possesses a distinctively long and flexible C-terminal region compared to other S100 proteins.
- Chaps molecules were observed to bind to the hinge region connecting the EF-hand motifs, indicating a potential target-binding site.
Conclusions:
- The flexible C-terminal region of hMRP14 may play a significant functional role.
- The identified binding site suggests a mechanism for target interaction in hMRP14 function.
- Structural insights into hMRP14 provide a basis for understanding the MRP8/14 hetero-complex and its role in inflammation and neutrophil adhesion.