Work

Leukocyte integrin α L β 2 headpiece structures: The αI domain, the pocket for the internal ligand, and concerted movements of its loops

Year: 2016

Type: article

Abstract: High-resolution crystal structures of the headpiece of lymphocyte function-associated antigen-1 (integrin αLβ2) reveal how the αI domain interacts with its platform formed by the α-subunit β-propeller and β-subunit βI domains. The αLβ2 structures compared with αXβ2 structures show that the αI domain, tethered through its N-linker and a disulfide to a stable β-ribbon pillar near the center of the platform, can undergo remarkable pivoting and tilting motions that appear buffered by N-glycan decorations that differ between αL and αX subunits. Rerefined β2 integrin structures reveal details including pyroglutamic acid at the β2 N terminus and bending within the EGF1 domain. Allostery is relayed to the αI domain by an internal ligand that binds to a pocket at the interface between the β-propeller and βI domains. Marked differences between the αL and αX subunit β-propeller domains concentrate near the binding pocket and αI domain interfaces. Remarkably, movement in allostery in the βI domain of specificity determining loop 1 (SDL1) causes concerted movement of SDL2 and thereby tightens the binding pocket for the internal ligand.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1601379113

Authors: Mehmet Sen, Timothy A. Springer

Institutions: Boston Children's Hospital, Harvard University, University of Houston

Language: English

Topic: Cell Adhesion Molecules Research

Subfield: Immunology and Allergy

Field: Medicine

Domain: Health Sciences

Open Access status: bronze

Funders: GlaxoSmithKline, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases

Awards: Lymphocyte Function Associated Antigens, Leukocyte Adhesion Receptors Mac-1 and P150,95, G5417538425, G6141339945, LYMPHOCYTE FUNCTION ASSOCIATED ANTIGENS