FHA domains bind phosphoThr peptides in signaling. We identified phosphoThr peptides from receptor-like kinases recognized by the FHA domain from the kinase-associated phosphatase in plant cell membranes (Ding et al., 2007, Biochemistry). One peptide widely rigidified this FHA domain, analogously to phosphoTyr peptide effects on the SH2 and PTB domains (Ding et al., 2005, Biochemistry). (This was supported by NSF  MCB0111589).

In MMP-12, we discovered that peptidic inhibitors trigger conformational change propagating through the catalytic domain (Bhaskaran et al., 2007, JMB).

Intriguingly, remote binding of elastin fragments to distant exosites of MMP-12 enhanced proteolytic digestion of elastin (Fulcher et al., 2011, Biochemistry). (These were supported by NIH GM057289).

We surmise that molecular recognition can run deep and wide.

Publications cited:

Bhaskaran R, Palmier MO, Bagegni NA, Liang X, Van Doren SR. Solution structure of inhibitor-free human metalloelastase (MMP-12) indicates an internal conformational adjustment. J Mol Biol. 2007 Dec 14;374(5):1333-44. https://doi.org/10.1016/j.jmb.2007.10.028

Ding Z, Lee GI, Liang X, Gallazzi F, Arunima A, Van Doren SR. PhosphoThr peptide binding globally rigidifies much of the FHA domain from Arabidopsis receptor kinase-associated protein phosphatase.Biochemistry. 2005 Aug 2;44(30):10119-34. https://pubs.acs.org/doi/10.1021/bi050414a

Ding Z, Wang H, Liang X, Morris ER, Gallazzi F, Pandit S, Skolnick J, Walker JC, Van Doren SR. Phosphoprotein and phosphopeptide interactions with the FHA domain from Arabidopsis kinase-associated protein phosphatase. Biochemistry. 2007 Mar 13;46(10):2684-96. https://pubs.acs.org/doi/10.1021/bi061763n

Fulcher YG, Van Doren SR. Remote exosites of the catalytic domain of matrix metalloproteinase-12 enhance elastin degradation. Biochemistry. 2011 Nov 8;50(44):9488-99. https://doi.org/10.1021/bi2009807