5X57

Structure of GAR domain of ACF7

Summary for 5X57

• Entry DOI: 10.2210/pdb5x57/pdb
• Descriptor: Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5, NICKEL (II) ION (3 entities in total)
• Functional Keywords: functional class, signaling protein
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform 2: Cytoplasm, cytoskeleton. Isoform 1: Cytoplasm: Q9UPN3
• Total number of polymer chains: 1
• Total formula weight: 9479.52

Authors

Yang, F.,Wang, T.,Zhang, Y.,Wu, X.Y. (deposition date: 2017-02-15, release date: 2017-07-05, Last modification date: 2024-03-27)

Primary citation

Ma, Y.,Yue, J.,Zhang, Y.,Shi, C.,Odenwald, M.,Liang, W.G.,Wei, Q.,Goel, A.,Gou, X.,Zhang, J.,Chen, S.Y.,Tang, W.J.,Turner, J.R.,Yang, F.,Liang, H.,Qin, H.,Wu, X.
ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics.
Nat Commun, 8:15375-15375, 2017

PubMed Abstract: In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro. With the mouse genetics approach, we show that ablation of ACF7 inhibits intestinal wound healing and greatly increases susceptibility to experimental colitis in mice. ACF7 level is also correlated with development and progression of ulcerative colitis (UC) in human patients. Together, our results reveal an important molecular mechanism whereby coordinated cytoskeletal dynamics contributes to cell adhesion regulation during intestinal wound repair and the development of IBD.

PubMed: 28541346
DOI: 10.1038/ncomms15375

Experimental method

X-RAY DIFFRACTION (1.45 Å)