2L91

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

2L91 の概要

• エントリーDOI: 10.2210/pdb2l91/pdb
• NMR情報: BMRB: 17433
• 分子名称: Integrin beta-3 (1 entity in total)
• 機能のキーワード: transmembrane segment, integrin, cell adhesion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05106
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4680.72

構造登録者

Schmidt, T.,Ulmer, T.S. (登録日: 2011-01-27, 公開日: 2011-12-21, 最終更新日: 2024-05-15)

主引用文献

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

実験手法

SOLUTION NMR