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Function and conformation analyses of an aspartate substitution of the invariant glycine in the integrin βI domain α1-α1' helix.

ABSTRACT: We showed that the αLβ2 integrin with the non-functional mutation G150D cannot be induced with Mg/EGTA to express the mAb KIM127 epitope, which reports the leg-extended conformation. We extended the study to the αIIbβ3, an integrin without an αI domain. The equivalent mutation, i.e. G161D, also resulted in an expressible, but non-adhesive αIIbβ3 integrin. An NMR study of synthetic peptides spanning the α1-α1' helix of the β3 I domain shows that both wild-type and mutant peptides are α-helical. However, whereas in the wild-type peptide this helix is continuous, the mutant presents a discontinuity, or kink, precisely at the site of mutation G161D. Our results suggest that the mutation may lock integrin heterodimers in a bent conformation that prevents integrin activation via conformational extension.

SUBMITTER: Guan S

PROVIDER: S-EPMC5613341 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Function and conformation analyses of an aspartate substitution of the invariant glycine in the integrin βI domain α1-α1' helix.

Guan Siyu S Tan Suet-Mien SM Li Yan Y Torres Jaume J Alex Law S K SK

Biochemistry and biophysics reports 20160620

We showed that the αLβ2 integrin with the non-functional mutation G150D cannot be induced with Mg/EGTA to express the mAb KIM127 epitope, which reports the leg-extended conformation. We extended the study to the αIIbβ3, an integrin without an αI domain. The equivalent mutation, i.e. G161D, also resulted in an expressible, but non-adhesive αIIbβ3 integrin. An NMR study of synthetic peptides spanning the α1-α1' helix of the β3 I domain shows that both wild-type and mutant peptides are α-helical. H ...[more]

PMID: 28955909

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