5HGJ

Structure of integrin alpha1beta1 and alpha2beta1 I-domains explain differential calcium-mediated ligand recognition

Summary for 5HGJ

• Entry DOI: 10.2210/pdb5hgj/pdb
• Descriptor: Integrin alpha-1, CALCIUM ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: integrin, signaling, rossman, i-domain, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 43921.21

Authors

Brown, K.L.,Banerjee, S.,Feigley, A.,Abe, H.,Blackwell, T.,Zent, R.,Pozzi, A.,Hudson, B.H. (deposition date: 2016-01-08, release date: 2017-04-12, Last modification date: 2024-03-06)

Primary citation

Brown, K.L.,Banerjee, S.,Feigley, A.,Abe, H.,Blackwell, T.S.,Pozzi, A.,Hudson, B.G.,Zent, R.
Salt-bridge modulates differential calcium-mediated ligand binding to integrin alpha 1- and alpha 2-I domains.
Sci Rep, 8:2916-2916, 2018

PubMed Abstract: Integrins are transmembrane cell-extracellular matrix adhesion receptors that impact many cellular functions. A subgroup of integrins contain an inserted (I) domain within the α-subunits (αI) that mediate ligand recognition where function is contingent on binding a divalent cation at the metal ion dependent adhesion site (MIDAS). Ca is reported to promote α1I but inhibit α2I ligand binding. We co-crystallized individual I-domains with MIDAS-bound Ca and report structures at 1.4 and 2.15 Å resolution, respectively. Both structures are in the "closed" ligand binding conformation where Ca induces minimal global structural changes. Comparisons with Mg-bound structures reveal Mg and Ca bind α1I in a manner sufficient to promote ligand binding. In contrast, Ca is displaced in the α2I domain MIDAS by 1.4 Å relative to Mg and unable to directly coordinate all MIDAS residues. We identified an E152-R192 salt bridge hypothesized to limit the flexibility of the α2I MIDAS, thus, reducing Ca binding. A α2I E152A construct resulted in a 10,000-fold increase in Mg and Ca binding affinity while increasing binding to collagen ligands 20%. These data indicate the E152-R192 salt bridge is a key distinction in the molecular mechanism of differential ion binding of these two I domains.

PubMed: 29440721
DOI: 10.1038/s41598-018-21231-1

Experimental method

X-RAY DIFFRACTION (1.399 Å)