Crystal structure of the FAT domain of Focal Adhesion Kinase
Identifiers
Symbol
Focal_AT
Pfam
PF03623
InterPro
IPR005189
SCOP2
1ktm / SCOPe / SUPFAM
Available protein structures:
Pfam
structures / ECOD
PDB
RCSB PDB; PDBe; PDBj
PDBsum
structure summary
In structural and cell biology, the focal adhesion targeting domain is a conserved protein domain that was first identified in focal adhesion kinase (FAK), also known as PTK2 protein tyrosine kinase 2 (PTK2).[1]
Focal adhesions are multi-protein intracellular signalling complexes that link the cellular actin microfilament cytoskeleton, through the cell membrane via transmembrane integrin proteins, to the extracellular matrix. Focal adhesions form and dissipate as cells attach and detach from matrix during cell adhesion and cell migration.[2]
The FAK focal adhesion targeting (FAT) domain is a C-terminal region necessary and sufficient for localizing FAK to focal adhesions, allowing FAK to regulate cell adhesion and migration by localizing its protein kinase activity at the junction of internal cytoskeleton and external cell attachment points. The crystal structure of FAT shows it to form a four-helix bundle that binds specifically to Leucine-Aspartate (LD)-repeat motif peptides in the related focal adhesion proteins paxillin (PXN), leupaxin (LPXN) and TGFB1I1/Hic-5.[1]
FAT domains with a similar 4-helix bundle structure are also found in other proteins that localize to paxillin-containing focal adhesions and are involved in cell adhesion and migration, including the FAK-related protein kinase PTK2B/FAK2/PYK2, and alpha-catenin, vinculin, Programmed cell death protein 10 (PDCD10)/Cerebral Cavernous Malformation protein 3 (CCM3) and GIT1/GIT2.[3]
^ abHayashi I, Vuori K, Liddington RC (February 2002). "The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin". Nat. Struct. Biol. 9 (2): 101–6. doi:10.1038/nsb755. PMID 11799401. S2CID 19881447.
^Burridge K, Fath K, Kelly T, Nuckolls G, Turner C (1988). "Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton". Annual Review of Cell Biology. 4: 487–525. doi:10.1146/annurev.cb.04.110188.002415. PMID 3058164.
^Alam T, Alazmi M, Gao X, Arold ST (June 2014). "How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs". Biochemical Journal. 460 (3): 317–329. doi:10.1042/BJ20140298. PMID 24870021.
and 23 Related for: Focal adhesion targeting region information
and cell biology, the focaladhesiontargeting domain is a conserved protein domain that was first identified in focaladhesion kinase (FAK), also known...
transmitted through the focaladhesion. A carboxy-terminal region of one hundred and fifty-nine amino acids, the focaladhesiontargeting domain (FAT), has...
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can...
tyrosine phosphatase-PEST, tubulin and serves as the targeting motif for focaladhesions. The N-terminal region of paxillin has five highly conserved leucine-rich...
cell-ECM adhesion, such as the formation of adherens junctions, tight junctions and focaladhesions. Adherens junctions are a type of cell-cell adhesion structure...
signal cascades since YpkA is targeted to the cytoplasmic side of the host cell membrane. YopH acts on host focaladhesion sites by dephosphorylating several...
transmembrane receptors that help cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that...
adhesion targeting (FAT) domain The FAT-like C-terminal domain is highly conserved in focaladhesion proteins, and sufficient for localizing focaladhesion kinase...
However, focaladhesions are quite more than simple anchors - their proteins have many roles in signaling. These proteins, such as focaladhesion kinase...
responsible for targeting integrin dimers to the appropriate subcellular locations, which in adhesive cells is mainly focaladhesions. Integrin beta-1...
chromosome 7. TES is a 47 kDa protein composed of 421 amino acids found at focaladhesions and is thought to have a role in regulation of cell motility. In addition...
forming multiple heterodimers, which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses...
JE (1995). "Identification and characterization of a novel related adhesionfocal tyrosine kinase (RAFTK) from megakaryocytes and brain". J. Biol. Chem...
cytoskeleton to adhesion proteins. In addition to F-actin, the N-terminal region of talin-1 binds layilin, β1- and β3-integrin, and focaladhesion kinase. Talin-1...
ribosylation factor-GTPase activating protein, with focaladhesion kinase contributes to the process of focaladhesion assembly". Molecular Biology of the Cell....
the affinity of integrins for the extracellular matrix and catalyzes focaladhesion-dependent signaling pathways, as well as reinforces the cytoskeletal-integrin...
cancer specific drug targeting [1]. Acting through several integrins and probably a few yet unknown other receptors Thy-1 mediates adhesion of leukocytes and...
adhesion of SW80 carcinoma cells to the third FN-III repeat of TN-C via the αvβ3 integrin receptor leads to cell spreading, phosphorylation of focal adhesion...
Unconventional myosins X, VIIa and XV, which are mutated in congenital deafness. Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling...
functions as an adhesion receptor due to its affinity to vitronectin, integrins and other proteases like PAI-1. The lack of the uPAR binding region in zebrafish...
called pp125, also referred to as focaladhesion kinase (FAK) is likely at hand in the influence of cellular focaladhesions, as indicated by an immunofluorescent...
domain-containing proline-rich protein, p85SPR, and its localization in focaladhesion". Biochemical and Biophysical Research Communications. 235 (3): 794–798...
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