Summary: Talin, middle domain
This is the Wikipedia entry entitled "Talin protein". More...
Does Pfam agree with the content of the Wikipedia entry ?
Editing Wikipedia articles
Before you edit for the first time
You should take a few minutes to view the following pages:
How your contribution will be recorded
Talin protein Edit Wikipedia article
|Talin, middle domain|
|Locus||Chr. 9 p23-p21|
|Locus||Chr. 15 q15-q21|
Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and alpha-actinin.
Integrin receptors are involved in the attachment of adherent cells to the extracellular matrix and of lymphocytes to other cells. In these situations, talin codistributes with concentrations of integrins in the plasma membrane. Furthermore, in vitro binding studies suggest that integrins bind to talin, although with low affinity. Talin also binds with high affinity to vinculin, another cytoskeletal protein concentrated at points of cell adhesion. Finally, talin is a substrate for the calcium-ion activated protease, calpain II, which is also concentrated at points of cell–substratum contact.
 Protein domains
Talin consists of a large C-terminal rod domain that contains bundles of alpha helices and an N-terminal FERM (band 4.1, ezrin, radixin, and moesin) domain with three subdomains: F1, F2, and F3. The F3 subdomain of the FERM domain contains the highest affinity integrin-binding site for integrin β tails and is sufficient to activate integrins.
 Middle domain
Talin also has a middle domain, which has a structure consisting of five alpha helices that fold into a bundle. It contains a Vinculin binding site (VBS) composed of a hydrophobic surface spanning five turns of helix four.
Activation of the VBS leads to the recruitment of Vinculin, talin to form a complex with the integrins which aids stable cell adhesion. Formation of the complex between VBS and Vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin.
 Vinculin binding site
human vinculin head (1-258) in complex with talin's vinculin binding site 3 (residues 1944-1969)
Vinculin binding sites are protein domains predominantly found in talin and talin-like molecules, enabling binding of vinculin to talin, stabilising integrin-mediated cell-matrix junctions. Talin, in turn, links integrins to the actin cytoskeleton.
The consensus sequence for Vinculin binding sites is LxxAAxxVAxxVxxLIxxA, with a secondary structure prediction of four amphipathic helices. The hydrophobic residues that define the VBS are themselves 'masked' and are buried in the core of a series of helical bundles that make up the talin rod.
 Activation the integrin αIIbβ3
- The talin F3 domain (surface representation; colored by charge), freed from its autoinhibitory interactions in the full-length protein, becomes available for binding to the integrin.
- F3 engages the membrane-distal part of the β3-integrin tail (in red), which becomes ordered, but the α–β integrin interactions that hold the integrin in the low-affinity conformation remain intact.
- In a subsequent step, F3 engages the membrane-proximal portion of the β3 tail while maintaining its membrane–distal interactions.
 Human proteins containing this domain
 See also
- Burridge K, Connell L (1983). "A new protein of adhesion plaques and ruffling membranes". J. Cell Biol. 97 (2): 359–67. doi:10.1083/jcb.97.2.359. PMC 2112532. PMID 6684120.
- Kupfer A, Singer SJ, Dennert G (1986). "On the mechanism of unidirectional killing in mixtures of two cytotoxic T lymphocytes. Unidirectional polarization of cytoplasmic organelles and the membrane-associated cytoskeleton in the effector cell". J. Exp. Med. 163 (3): 489–98. doi:10.1084/jem.163.3.489. PMC 2188060. PMID 3081676.
- Burn P, Kupfer A, Singer SJ (1988). "Dynamic membrane-cytoskeletal interactions: specific association of integrin and talin arises in vivo after phorbol ester treatment of peripheral blood lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 85 (2): 497–501. doi:10.1073/pnas.85.2.497. PMC 279577. PMID 3124107.
- Alan D. Michelson (2006). Platelets, Second Edition. Boston: Academic Press. ISBN 0-12-369367-5.
- Hynes RO (1987). "Integrins: a family of cell surface receptors". Cell 48 (4): 549–54. doi:10.1016/0092-8674(87)90233-9. PMID 3028640.
- Ruoslahti E, Pierschbacher MD (1987). "New perspectives in cell adhesion: RGD and integrins". Science 238 (4826): 491–7. doi:10.1126/science.2821619. PMID 2821619.
- Chen WT, Hasegawa E, Hasegawa T, Weinstock C, Yamada KM (1985). "Development of cell surface linkage complexes in cultured fibroblasts". J. Cell Biol. 100 (4): 1103–14. doi:10.1083/jcb.100.4.1103. PMC 2113771. PMID 3884631.
- Kupfer A, Singer SJ (1989). "The specific interaction of helper T cells and antigen-presenting B cells. IV. Membrane and cytoskeletal reorganizations in the bound T cell as a function of antigen dose". J. Exp. Med. 170 (5): 1697–713. doi:10.1084/jem.170.5.1697. PMC 2189515. PMID 2530300.
- Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K (1986). "Interaction of plasma membrane fibronectin receptor with talin—a transmembrane linkage". Nature 320 (6062): 531–3. doi:10.1038/320531a0. PMID 2938015.
- Burridge K, Mangeat P (1984). "An interaction between vinculin and talin". Nature 308 (5961): 744–6. doi:10.1038/308744a0. PMID 6425696.
- Geiger B (1979). "A 130K protein from chicken gizzard: its localization at the termini of microfilament bundles in cultured chicken cells". Cell 18 (1): 193–205. doi:10.1016/0092-8674(79)90368-4. PMID 574428.
- Fox JE, Goll DE, Reynolds CC, Phillips DR (1985). "Identification of two proteins (actin-binding protein and P235) that are hydrolyzed by endogenous Ca2+-dependent protease during platelet aggregation". J. Biol. Chem. 260 (2): 1060–6. PMID 2981831.
- Beckerle MC, Burridge K, DeMartino GN, Croall DE (1987). "Colocalization of calcium-dependent protease II and one of its substrates at sites of cell adhesion". Cell 51 (4): 569–77. doi:10.1016/0092-8674(87)90126-7. PMID 2824061.
- Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low PS, Rouleau GA, Mohandas N, Chasis JA, Conboy JG, Gascard P, Takakuwa Y, Huang SC, Benz EJ, Bretscher A, Fehon RG, Gusella JF, Ramesh V, Solomon F, Marchesi VT, Tsukita S, Tsukita S, Hoover KB (1998). "The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane". Trends Biochem. Sci. 23 (8): 281–2. doi:10.1016/S0968-0004(98)01237-7. PMID 9757824.
- García-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID, Ginsberg MH, Liddington RC (2003). "Structural determinants of integrin recognition by talin". Mol. Cell 11 (1): 49–58. doi:10.1016/S1097-2765(02)00823-7. PMID 12535520.
- Papagrigoriou E, Gingras AR, Barsukov IL, Bate N, Fillingham IJ, Patel B, Frank R, Ziegler WH, Roberts GC, Critchley DR, Emsley J (2004). "Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle". EMBO J. 23 (15): 2942–51. doi:10.1038/sj.emboj.7600285. PMC 514914. PMID 15272303.
- Rees DJ, Ades SE, Singer SJ, Hynes RO (1990). "Sequence and domain structure of talin". Nature 347 (6294): 685–9. doi:10.1038/347685a0. PMID 2120593.
- Calderwood DA, Yan B, de Pereda JM, Alvarez BG, Fujioka Y, Liddington RC, Ginsberg MH (2002). "The phosphotyrosine binding-like domain of talin activates integrins". J. Biol. Chem. 277 (24): 21749–58. doi:10.1074/jbc.M111996200. PMID 11932255.
- Gingras AR, Vogel KP, Steinhoff HJ, Ziegler WH, Patel B, Emsley J, Critchley DR, Roberts GC, Barsukov IL (February 2006). "Structural and dynamic characterization of a vinculin binding site in the talin rod". Biochemistry 45 (6): 1805–17. doi:10.1021/bi052136l. PMID 16460027.
- Wegener KL, Partridge AW, Han J, Pickford AR, Liddington RC, Ginsberg MH, Campbell ID (2007). "Structural basis of integrin activation by talin". Cell 128 (1): 171–82. doi:10.1016/j.cell.2006.10.048. PMID 17218263.
- MBInfo: Talin
- MBInfo: Talin activates integrins
- Talin-1 UniProtKB/Swiss-Prot entry Q9Y490
- Talin substrate for calpain – PMAP The Proteolysis Map animation.
- Talin-1 Info with links in the Cell Migration Gateway
- Talin-2 Info with links in the Cell Migration Gateway
- Integrins at the US National Library of Medicine Medical Subject Headings (MeSH)
Talin, middle domain Provide feedback
Members of this family adopt a structure consisting of five alpha helices that fold into a bundle. They contain a Vinculin binding site (VBS) composed of a hydrophobic surface spanning five turns of helix four. Activation of the VBS causes subsequent recruitment of Vinculin, which enables maturation of small integrin/talin complexes into more stable adhesions. Formation of the complex between VBS and Vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin .
Papagrigoriou E, Gingras AR, Barsukov IL, Bate N, Fillingham IJ, Patel B, Frank R, Ziegler WH, Roberts GC, Critchley DR, Emsley J; , EMBO J. 2004;23:2942-2951.: Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle. PUBMED:15272303 EPMC:15272303
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR015224
This domain adopts a structure consisting of five alpha helices that fold into a bundle. It contains a Vinculin binding site (VBS) composed of a hydrophobic surface spanning five turns of helix four. Activation of the VBS causes subsequent recruitment of Vinculin, which enables maturation of small integrin/talin complexes into more stable adhesions. Formation of the complex between VBS and Vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin [PUBMED:15272303].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||ruffle (GO:0001726)|
|focal adhesion (GO:0005925)|
|Molecular function||structural constituent of cytoskeleton (GO:0005200)|
|Biological process||cytoskeletal anchoring at plasma membrane (GO:0007016)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Number in seed:||6|
|Number in full:||194|
|Average length of the domain:||157.90 aa|
|Average identity of full alignment:||59 %|
|Average coverage of the sequence by the domain:||6.87 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||5|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Talin_middle domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...