2L91

Structure of the Integrin beta3 (A711P,K716A) Transmembrane Segment

Summary for 2L91

• Entry DOI: 10.2210/pdb2l91/pdb
• NMR Information: BMRB: 17433
• Descriptor: Integrin beta-3 (1 entity in total)
• Functional Keywords: transmembrane segment, integrin, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P05106
• Total number of polymer chains: 1
• Total formula weight: 4680.72

Authors

Schmidt, T.,Ulmer, T.S. (deposition date: 2011-01-27, release date: 2011-12-21, Last modification date: 2024-05-15)

Primary citation

Kim, C.,Schmidt, T.,Cho, E.G.,Ye, F.,Ulmer, T.S.,Ginsberg, M.H.
Basic amino-acid side chains regulate transmembrane integrin signalling.
Nature, 481:209-213, 2012

PubMed Abstract: Side chains of Lys/Arg near transmembrane domain (TMD) membrane-water interfaces can 'snorkel', placing their positive charge near negatively charged phospholipid head groups; however, snorkelling's functional effects are obscure. Integrin β TMDs have such conserved basic amino acids. Here we use NMR spectroscopy to show that integrin β(3)(Lys 716) helps determine β(3) TMD topography. The α(ΙΙb)β(3) TMD structure indicates that precise β(3) TMD crossing angles enable the assembly of outer and inner membrane 'clasps' that hold the αβ TMD together to limit transmembrane signalling. Mutation of β(3)(Lys 716) caused dissociation of α(ΙΙb)β(3) TMDs and integrin activation. To confirm that altered topography of β(3)(Lys 716) mutants activated α(ΙΙb)β(3), we used directed evolution of β(3)(K716A) to identify substitutions restoring default state. Introduction of Pro(711) at the midpoint of β(3) TMD (A711P) increased α(ΙΙb)β(3) TMD association and inactivated integrin α(ΙΙb)β(3)(A711P,K716A). β(3)(Pro 711) introduced a TMD kink of 30 ± 1° precisely at the border of the outer and inner membrane clasps, thereby decoupling the tilt between these segments. Thus, widely occurring snorkelling residues in TMDs can help maintain TMD topography and membrane-embedding, thereby regulating transmembrane signalling.

PubMed: 22178926
DOI: 10.1038/nature10697

Experimental method

SOLUTION NMR