Dataset Information

Structure and binding interface of the cytosolic tails of ?X?2 integrin.

ABSTRACT:

Background

Integrins are signal transducer proteins involved in a number of vital physiological processes including cell adhesion, proliferation and migration. Integrin molecules are hetero-dimers composed of two distinct subunits, ? and ?. In humans, 18 ? and 8 ? subunits are combined into 24 different integrin molecules. Each of the subunit comprises a large extracellular domain, a single pass transmembrane segment and a cytosolic tail (CT). The CTs of integrins are vital for bidirectional signal transduction and in maintaining the resting state of the receptors. A large number of intracellular proteins have been found to interact with the CTs of integrins linking integrins to the cytoskeleton.

Methodology/principal findings

In this work, we have investigated structure and interactions of CTs of the leukocyte specific integrin ?X?2. We determined the atomic resolution structure of a myristoylated CT of ?X in perdeuterated dodecylphosphocholine (DPC) by NMR spectroscopy. Our results reveal that the 35-residue long CT of ?X adopts an ?-helical conformation for residues F4-N17 at the N-terminal region. The remaining residues located at the C-terminal segment of ?X delineate a long loop of irregular conformations. A segment of the loop maintains packing interactions with the helical structure by an extended non-polar surface of the ?X CT. Interactions between ?X and ?2 CTs are demonstrated by (15)N-(1)H HSQC NMR experiments. We find that residues constituting the polar face of the helical conformation of ?X are involved in interactions with the N-terminal residues of ?2 CT. A docked structure of the CT complex indicates that a network of polar and/or salt-bridge interactions may sustain the heteromeric interactions.

Conclusions/significance

The current study provides important insights into the conservation of interactions and structures among different CTs of integrins.

SUBMITTER: Chua GL

PROVIDER: S-EPMC3406025 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Structure and binding interface of the cytosolic tails of αXβ2 integrin.

Chua Geok-Lin GL Tang Xiao-Yan XY Patra Alok Tanala AT Tan Suet-Mien SM Bhattacharjya Surajit S

PloS one 20120726 7

<h4>Background</h4>Integrins are signal transducer proteins involved in a number of vital physiological processes including cell adhesion, proliferation and migration. Integrin molecules are hetero-dimers composed of two distinct subunits, α and β. In humans, 18 α and 8 β subunits are combined into 24 different integrin molecules. Each of the subunit comprises a large extracellular domain, a single pass transmembrane segment and a cytosolic tail (CT). The CTs of integrins are vital for bidirecti ...[more]

PMID: 22844534

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