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Title: Leukocyte integrin αLβ2 headpiece structures: The αI domain, the pocket for the internal ligand, and concerted movements of its loops

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2]
  1. Harvard Medical School, Boston, MA (United States); Univ. of Houston, TX (United States)
  2. Harvard Medical School, Boston, MA (United States)
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Institutes of Health (NIH)
Grant/Contract Number:
NCI CA031798
OSTI ID:
1252752
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 11; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 33 works
Citation information provided by
Web of Science

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Cited By (11)

Solving the riddle: Unraveling the mechanisms of blocking the binding of leukotoxin by therapeutic antagonists in periodontal diseases: ABDULLAHI et al. journal August 2018
Regulation of cell adhesion: a collaborative effort of integrins, their ligands, cytoplasmic actors, and phosphorylation journal January 2019
Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration journal December 2017
General structural features that regulate integrin affinity revealed by atypical αVβ8 journal December 2019
Salt-bridge modulates differential calcium-mediated ligand binding to integrin α1- and α2-I domains journal February 2018
Molecular mechanism of leukocidin GH–integrin CD11b/CD18 recognition and species specificity journal December 2019
Research advances on structure and biological functions of integrins journal July 2016
Molecular mechanism of leukocidin GH–integrin CD11b/CD18 recognition and species specificity text January 2020
Measuring Integrin Conformational Change on the Cell Surface with Super-Resolution Microscopy journal February 2018
Cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment journal November 2018
Structural Immunology of Complement Receptors 3 and 4 journal November 2018

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