Structure of the Integrin β3 Transmembrane Segment in Phospholipid Bicelles and Detergent Micelles

2005/01/01 by Tong-Lay Lau, Tong‐Lay Lau, Anthony W. Partridge +6 · 121 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Computer Science · Medicine · #Aqueous solution #Bilayer #Biochemistry #Biology #Biophysics #Cell Adhesion Molecules Research #Chemistry #Crystallography #Distributed and Parallel Computing Systems #Distributed systems and fault tolerance #Helix (gastropod) #Integral membrane protein #Integrin #Lipid Membrane Structure and Behavior #Lipid bilayer #Lipid bilayer phase behavior #Membrane #Membrane protein #Micelle #Model lipid bilayer #Monoclonal and Polyclonal Antibodies Research #Organic chemistry #Phospholipid #Protein–lipid interaction #Receptor #Service-Oriented Architecture and Web Services #Transmembrane domain #Transmembrane protein

paper · doi:10.1021/bi800107a

published in Biochemistry 47(13), 4008-4016 (American Chemical Society)

openalex publication_date 2008/03/06 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/26

Abstract

Integrin adhesion receptors transduce bidirectional signals across the plasma membrane, with the integrin transmembrane domains acting as conduits in this process. Here, we report the first high-resolution structure of an integrin transmembrane domain. To assess the influence of the membrane model system, structure determinations of the beta3 integrin transmembrane segment and flanking sequences were carried out in both phospholipid bicelles and detergent micelles. In bicelles, a 30-residue linear alpha-helix, encompassing residues I693-H772, is adopted, of which I693-I721 appear embedded in the hydrophobic bicelle core. This relatively long transmembrane helix implies a pronounced helix tilt within a typical lipid bilayer, which facilitates the snorkeling of K716's charged side chain out of the lipid core while simultaneously immersing hydrophobic L717-I721 in the membrane. A shortening of bicelle lipid hydrocarbon tails does not lead to the transfer of L717-I721 into the aqueous phase, suggesting that the reported embedding represents the preferred beta3 state. The nature of the lipid headgroup affected only the intracellular part of the transmembrane helix, indicating that an asymmetric lipid distribution is not required for studying the beta3 transmembrane segment. In the micelle, residues L717-I721 are also embedded but deviate from linear alpha-helical conformation in contrast to I693-K716, which closely resemble the bicelle structure.

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