5FPI

Mu2 adaptin subunit of the AP2 adaptor (C-terminal domain) complexed with Integrin alpha4 internalisation peptide QYKSILQE

Summary for 5FPI

• Entry DOI: 10.2210/pdb5fpi/pdb
• Descriptor: AP-2 COMPLEX SUBUNIT MU, INTEGRIN ALPHA-4 SUBUNIT (3 entities in total)
• Functional Keywords: endocytosis, clathrin adaptor
• Biological source: RATTUS NORVEGICUS (NORWAY RAT); More
• Cellular location: Cell membrane : P84092
• Total number of polymer chains: 2
• Total formula weight: 52053.25

Authors

Owen, D.J.,Evans, P.R.,Ivaska, J. (deposition date: 2015-11-30, release date: 2016-01-20, Last modification date: 2024-01-10)

Primary citation

De Franceschi, N.,Arjonen, A.,Elkhatib, N.,Denessiouk, K.,Wrobel, A.G.,Wilson, T.A.,Pouwels, J.,Montagnac, G.,Owen, D.J.,Ivaska, J.
Selective Integrin Endocytosis is Driven by Alpha Chain:Ap2 Interactions
Nat.Struct.Mol.Biol., 23:172-, 2016

PubMed Abstract: Integrins are heterodimeric cell-surface adhesion molecules comprising one of 18 possible α-chains and one of eight possible β-chains. They control a range of cell functions in a matrix- and ligand-specific manner. Integrins can be internalized by clathrin-mediated endocytosis (CME) through β subunit-based motifs found in all integrin heterodimers. However, whether specific integrin heterodimers can be selectively endocytosed was unknown. Here, we found that a subset of α subunits contain an evolutionarily conserved and functional YxxΦ motif directing integrins to selective internalization by the most abundant endocytic clathrin adaptor, AP2. We determined the structure of the human integrin α4-tail motif in complex with the AP2 C-μ2 subunit and confirmed the interaction by isothermal titration calorimetry. Mutagenesis of the motif impaired selective heterodimer endocytosis and attenuated integrin-mediated cell migration. We propose that integrins evolved to enable selective integrin-receptor turnover in response to changing matrix conditions.

PubMed: 26779610
DOI: 10.1038/NSMB.3161

Experimental method

X-RAY DIFFRACTION (2.77 Å)