7ceb | pdb_00007ceb

Crystal structure of alpha6beta1 integrin headpiece

Structural highlights

7ceb is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.89Å
Ligands:	CA, MG, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ITA6_HUMAN Junctional epidermolysis bullosa with pyloric atresia. The disease is caused by variants affecting the gene represented in this entry.

Function

ITA6_HUMAN Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (By similarity). Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464).[UniProtKB:Q61739]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Recognition of laminin by integrin receptors is central to the epithelial cell adhesion to basement membrane, but the structural background of this molecular interaction remained elusive. Here, we report the structures of the prototypic laminin receptor alpha6beta1 integrin alone and in complex with three-chain laminin-511 fragment determined via crystallography and cryo-electron microscopy, respectively. The laminin-integrin interface is made up of several binding sites located on all five subunits, with the laminin gamma1 chain C-terminal portion providing focal interaction using two carboxylate anchor points to bridge metal-ion dependent adhesion site of integrin beta1 subunit and Asn189 of integrin alpha6 subunit. Laminin alpha5 chain also contributes to the affinity and specificity by making electrostatic interactions with large surface on the beta-propeller domain of alpha6, part of which comprises an alternatively spliced X1 region. The propeller sheet corresponding to this region shows unusually high mobility, suggesting its unique role in ligand capture.

Structural mechanism of laminin recognition by integrin.,Arimori T, Miyazaki N, Mihara E, Takizawa M, Taniguchi Y, Cabanas C, Sekiguchi K, Takagi J Nat Commun. 2021 Jun 29;12(1):4012. doi: 10.1038/s41467-021-24184-8. PMID:34188035^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ieguchi K, Fujita M, Ma Z, Davari P, Taniguchi Y, Sekiguchi K, Wang B, Takada YK, Takada Y. Direct binding of the EGF-like domain of neuregulin-1 to integrins ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB signaling. J Biol Chem. 2010 Oct 8;285(41):31388-98. PMID:20682778 doi:10.1074/jbc.M110.113878
↑ Fujita M, Ieguchi K, Davari P, Yamaji S, Taniguchi Y, Sekiguchi K, Takada YK, Takada Y. Cross-talk between integrin α6β4 and insulin-like growth factor-1 receptor (IGF1R) through direct α6β4 binding to IGF1 and subsequent α6β4-IGF1-IGF1R ternary complex formation in anchorage-independent conditions. J Biol Chem. 2012 Apr 6;287(15):12491-500. PMID:22351760 doi:10.1074/jbc.M111.304170
↑ Cedano Prieto DM, Cheng Y, Chang CC, Yu J, Takada YK, Takada Y. Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling. PLoS One. 2017 Sep 5;12(9):e0184285. PMID:28873464 doi:10.1371/journal.pone.0184285
↑ Arimori T, Miyazaki N, Mihara E, Takizawa M, Taniguchi Y, Cabañas C, Sekiguchi K, Takagi J. Structural mechanism of laminin recognition by integrin. Nat Commun. 2021 Jun 29;12(1):4012. PMID:34188035 doi:10.1038/s41467-021-24184-8

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OCA

[1] Ieguchi K, Fujita M, Ma Z, Davari P, Taniguchi Y, Sekiguchi K, Wang B, Takada YK, Takada Y. Direct binding of the EGF-like domain of neuregulin-1 to integrins ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB signaling. J Biol Chem. 2010 Oct 8;285(41):31388-98. PMID:20682778 doi:10.1074/jbc.M110.113878

[2] Fujita M, Ieguchi K, Davari P, Yamaji S, Taniguchi Y, Sekiguchi K, Takada YK, Takada Y. Cross-talk between integrin α6β4 and insulin-like growth factor-1 receptor (IGF1R) through direct α6β4 binding to IGF1 and subsequent α6β4-IGF1-IGF1R ternary complex formation in anchorage-independent conditions. J Biol Chem. 2012 Apr 6;287(15):12491-500. PMID:22351760 doi:10.1074/jbc.M111.304170

[3] Cedano Prieto DM, Cheng Y, Chang CC, Yu J, Takada YK, Takada Y. Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling. PLoS One. 2017 Sep 5;12(9):e0184285. PMID:28873464 doi:10.1371/journal.pone.0184285

[4] Arimori T, Miyazaki N, Mihara E, Takizawa M, Taniguchi Y, Cabañas C, Sekiguchi K, Takagi J. Structural mechanism of laminin recognition by integrin. Nat Commun. 2021 Jun 29;12(1):4012. PMID:34188035 doi:10.1038/s41467-021-24184-8

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7ceb | pdb_00007ceb

Crystal structure of alpha6beta1 integrin headpiece

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

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