Related Experiment Video
Updated: Jun 24, 2026
06:45
Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling
Tong-Lay Lau1, Chungho Kim, Mark H Ginsberg
1Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
The EMBO Journal
|March 13, 2009
Summary
Researchers revealed the structure of the integrin alphaIIbbeta3 transmembrane (TM) complex, uncovering how its subunits associate and dissociate to enable bi-directional cell signaling. This finding clarifies a key mechanism in cell communication.
Area of Science:
- Biochemistry
- Structural Biology
- Cell Biology
Background:
- Integrin adhesion receptors are crucial for cell functions like migration and survival.
- Bi-directional signaling across the plasma membrane is mediated by integrins.
- Transmembrane (TM) subunit association and dissociation are hypothesized to be key to integrin signaling.
Purpose of the Study:
- To determine the structure of the integrin alphaIIbbeta3 TM complex.
- To elucidate the structural basis of TM signaling, specifically the transition between associated and dissociated states.
Main Methods:
- X-ray crystallography to determine the structure of the integrin alphaIIbbeta3 TM complex.
- Structure-based site-directed mutagenesis to investigate subunit interactions.
- Lipid embedding estimates to assess stability within the membrane.
Main Results:
- The integrin alphaIIbbeta3 TM complex is stabilized by glycine-packing interactions in the extracellular leaflet.
- Unique hydrophobic and electrostatic bridges mediate an asymmetric association between alphaIIb and beta3 TM helices in the intracellular leaflet.
- The study provides the first structure of a heterodimeric TM receptor complex.
Conclusions:
- The unique structure of the integrin alphaIIbbeta3 TM complex explains its role in bi-directional signaling.
- This structural insight provides a foundation for understanding integrin TM signaling mechanisms.
Related Concept Videos
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:09Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
01:25Structure of Cadherins
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...