The molecular basis of talin2's high affinity toward β1-integrin

Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang Guo Zhan, Cai Huang

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10 Scopus citations


Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β-integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with Cys diminished that of talin2. Further computational modeling analysis shows that talin2 S339 formed a hydrogen bond with E353, which is critical for inducing key hydrogen bonds between talin2 N326 and β1-integrin R760, and between talin2 K327 and β1-integrin D759. Mutation at any of these residues significantly diminished the interaction of talin2 with β1- integrin tails. These hydrogen bonds were not observed in talin1/β1-integrin, but did exist in talin1 C336S/β1-integrin complex. These results suggest that talin2 S339 forms a hydrogen bond with E353 to mediate its high affinity to β1-integrin.

Original languageEnglish
Article number41989
JournalScientific Reports
StatePublished - Feb 3 2017

Bibliographical note

Funding Information:
We thank Dr. Naser Jafari for his critical reading and Ms. Heather Russell-Simmons and Danielle L. Story for their editing of this manuscript. This work was supported by start-up funds from Markey Cancer Center, University of Kentucky and American Cancer Society Research Scholar Grant RSG-13-184-01CSM (to CH).

Publisher Copyright:
© The Author(s) 2017.

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