The interface between the EGF1 and EGF2 domains is critical in integrin affinity regulation

It has been proposed that integrins adopt a bent, closed conformation with low ligand binding capability at resting state and switch into an extended, open conformation upon activation or interacting with extracellular matrix (ECM) ligand. In this study, we addressed how integrin conformational chan...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular biochemistry 2018-09, Vol.119 (9), p.7264-7273
Main Authors: Hu, Ping, Luo, Bing‐Hao
Format: Article
Language:English
Subjects:
Affinity
Binding
chimera
Chimeras
Conformation
conformational change
Crystal structure
Domains
EGF domain
Epidermal growth factor
Extracellular matrix
Growth factors
integrin
Integrins
Ligands
Nucleotide sequence
Signaling
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:It has been proposed that integrins adopt a bent, closed conformation with low ligand binding capability at resting state and switch into an extended, open conformation upon activation or interacting with extracellular matrix (ECM) ligand. In this study, we addressed how integrin conformational change at the β genu affects ligand binding and signaling. We discovered that swapping of the β3 epidermal growth factor‐like (EGF) domain 1 and 2 with that of β8 greatly promoted ligand binding in β3β8 chimeras. Sequence alignment indicated that β8 integrin uniquely lacks the interface between the EGF1 and 2. Disrupting this interface of the β3 integrin increased integrin ligand binding. Furthermore, the interface is critical for integrin affinity regulation but not downstream outside‐in signaling. We discovered that the interface between β3 integrin EGF1 and 2 domains plays an important role in maintaining the integrin in inactive state with low ligand binding capacity. By using chimeric study and mutagenesis, we identified the C‐terminal region on the EGF1 domain that regulates integrin affinity state.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.26921