Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
6  structures 87  species 1  interaction 194  sequences 31  architectures

Family: Talin_middle (PF09141)

Summary: Talin, middle domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Talin protein". More...

Talin protein Edit Wikipedia article

Talin, middle domain
Identifiers
Symbol Talin_middle
Pfam PF09141
InterPro IPR015224
SCOP 1sj7
SUPERFAMILY 1sj7
talin 1
Identifiers
Symbol TLN1
Alt. symbols TLN
Entrez 7094
HUGO 11845
OMIM 186745
RefSeq NM_006289
UniProt Q9Y490
Other data
Locus Chr. 9 p23-p21
talin 2
Identifiers
Symbol TLN2
Entrez 83660
HUGO 15447
OMIM 607349
RefSeq NM_015059
UniProt Q9Y4G6
Other data
Locus Chr. 15 q15-q21

Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact[1] and, in lymphocytes, at cell–cell contacts.[2][3] Discovered in 1983 by Keith Burridge and colleagues,[1] 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.[4]

Integrin receptors are involved in the attachment of adherent cells to the extracellular matrix[5][6] and of lymphocytes to other cells. In these situations, talin codistributes with concentrations of integrins in the plasma membrane.[7][8] Furthermore, in vitro binding studies suggest that integrins bind to talin, although with low affinity.[9] Talin also binds with high affinity to vinculin,[10] another cytoskeletal protein concentrated at points of cell adhesion.[11] Finally, talin is a substrate for the calcium-ion activated protease, calpain II,[12] which is also concentrated at points of cell–substratum contact.[13]

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.[14][15][16][17] The F3 subdomain of the FERM domain contains the highest affinity integrin-binding site for integrin β tails and is sufficient to activate integrins.[18]

Middle domain

Structure

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.

Function

Activation of the VBS leads to the recruitment of vinculin 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.[16]

Vinculin binding site

VBS
PDB 1rkc EBI.jpg
human vinculin head (1-258) in complex with talin's vinculin binding site 3 (residues 1944-1969)
Identifiers
Symbol VBS
Pfam PF08913
InterPro IPR015009

Function

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.

Structure

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.[19]

Activation the integrin αIIbβ3

Model of talin-induced integrin activation

A structure–function analysis reported recently[20] provides a cogent structural model (see top right) to explain talin-dependent integrin activation in three steps:

  1. 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.
  2. 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.
  3. 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

TLN1; TLN2;

See also

References

  1. ^ a b 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Alan D. Michelson (2006). Platelets, Second Edition. Boston: Academic Press. ISBN 0-12-369367-5. 
  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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ Burridge K, Mangeat P (1984). "An interaction between vinculin and talin". Nature 308 (5961): 744–6. doi:10.1038/308744a0. PMID 6425696. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ a b 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. 
  17. ^ 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. 
  18. ^ 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. 
  19. ^ 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. 
  20. ^ 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. 

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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 [1].

Literature references

  1. 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].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(6)
Full
(194)
Representative proteomes NCBI
(161)
Meta
(0)
RP15
(33)
RP35
(42)
RP55
(70)
RP75
(108)
Jalview View  View  View  View  View  View  View   
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(6)
Full
(194)
Representative proteomes NCBI
(161)
Meta
(0)
RP15
(33)
RP35
(42)
RP55
(70)
RP75
(108)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(6)
Full
(194)
Representative proteomes NCBI
(161)
Meta
(0)
RP15
(33)
RP35
(42)
RP55
(70)
RP75
(108)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: pdb_1sj7
Previous IDs: none
Type: Domain
Author: Sammut SJ
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 35.3 25.2
Noise cut-off 24.9 23.7
Model length: 161
Family (HMM) version: 5
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

Talin_middle

Structures

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...