4Z6G

Structure of NT domain

Summary for 4Z6G

• Entry DOI: 10.2210/pdb4z6g/pdb
• Descriptor: Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5, PHOSPHATE ION (3 entities in total)
• Functional Keywords: cytoskeleton, cell migration, microtubule, focal adhesion, cell adhesion
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform 2: Cytoplasm, cytoskeleton. Isoform 1: Cytoplasm: Q9UPN3
• Total number of polymer chains: 1
• Total formula weight: 41003.61

Authors

Yang, F.,Zhang, Y. (deposition date: 2015-04-05, release date: 2016-04-06, Last modification date: 2023-11-08)

Primary citation

Yue, J.,Zhang, Y.,Liang, W.G.,Gou, X.,Lee, P.,Liu, H.,Lyu, W.,Tang, W.J.,Chen, S.Y.,Yang, F.,Liang, H.,Wu, X.
In vivo epidermal migration requires focal adhesion targeting of ACF7.
Nat Commun, 7:11692-11692, 2016

PubMed Abstract: Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7's NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essential for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Together, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement.

PubMed: 27216888
DOI: 10.1038/ncomms11692

Experimental method

X-RAY DIFFRACTION (2.654 Å)