Force-Induced Unfolding of Leucine-Rich Repeats of Glycoprotein Ibα Strengthens Ligand Interaction

Lining Ju, Jizhong Lou, Yunfeng Chen, Zhenhai Li, Cheng Zhu

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Leucine-rich repeat (LRR) is a versatile motif widely present in adhesive proteins and signal-transducing receptors. The concave structure formed by a group of LRRs is thought to facilitate binding to globular protein domains with increased affinities. However, little is known about the conformational dynamics of LRRs in such a structure, e.g., whether and how force induces conformational changes in LRRs to regulate protein binding and signal transduction. Here we investigated the platelet glycoprotein Ibα (GPIbα), a demonstrated mechanoreceptor with known crystal structures for the N-terminal domain (GPIbαN), as a model for LRR-containing proteins using a combined method of steered molecular dynamics simulations and single-molecule force spectroscopy with a biomembrane force probe. We found that force-induced unfolding of GPIbαN starts with LRR2-4 and propagates to other LRRs. Importantly, force-dependent lifetimes of individual VWF-A1 bonds with GPIbα are prolonged after LRR unfolding. Enhancement of protein-protein interactions by force-induced LRR unfolding may be a phenomenon of interest in biology.

Original languageEnglish (US)
Pages (from-to)1781-1784
Number of pages4
JournalBiophysical journal
Issue number9
StatePublished - Nov 3 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics


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