View source for 6mfs


==Mouse talin1 residues 1-138 fused to residues 169-400 in complex with phosphatidylinositol 4,5-bisphosphate (PIP2)==
<StructureSection load='6mfs' size='340' side='right'caption='[[6mfs]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mfs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MFS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6mfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mfs OCA], [https://pdbe.org/6mfs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mfs RCSB], [https://www.ebi.ac.uk/pdbsum/6mfs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mfs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TLN1_MOUSE TLN1_MOUSE] Probably involved in connections of major cytoskeletal structures to the plasma membrane. High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts.
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== Publication Abstract from PubMed ==
Multicellular organisms have well-defined, tightly regulated mechanisms for cell adhesion. Heterodimeric alphabeta integrin receptors play central roles in this function and regulate processes for normal cell functions, including signaling, cell migration, and development, binding to the extracellular matrix, and senescence. They are involved in hemostasis and the immune response, participate in leukocyte function, and have biological implications in angiogenesis and cancer. Proper control of integrin activation for cellular communication with the external environment requires several physiological processes. Perturbation of these equilibria may lead to constitutive integrin activation that results in bleeding disorders. Furthermore, integrins play key roles in cancer progression and metastasis in which certain tumor types exhibit higher levels of various integrins. Thus, the integrin-associated signaling complex is important for cancer therapy development. During inside-out signaling, the cytoskeletal protein talin plays a key role in regulating integrin affinity whereby the talin head domain activates integrin by binding to the cytoplasmic tail of beta-integrin and acidic membrane phospholipids. To understand the mechanism of integrin activation by talin, we determined the crystal structure of the talin head domain bound to the acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), allowing us to design a lipid-binding-deficient talin mutant. Our confocal microscopy with talin knockout cells suggests that the talin-cell membrane interaction seems essential for focal adhesion formation and stabilization. Basal integrin activation in Chinese hamster ovary cells suggests that the lipid-binding-deficient talin mutant inhibits integrin activation. Thus, membrane attachment of talin seems necessary for integrin activation and focal adhesion formation.

The interaction of talin with the cell membrane is essential for integrin activation and focal adhesion formation.,Chinthalapudi K, Rangarajan ES, Izard T Proc Natl Acad Sci U S A. 2018 Sep 25. pii: 1806275115. doi:, 10.1073/pnas.1806275115. PMID:30254158<ref>PMID:30254158</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mfs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Talin|Talin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Chinthalapudi K]]
[[Category: Izard T]]
[[Category: Rangarajan ES]]