Table 2.

Structural basis of GF binding preferences by ActRII, ActRIIB, ALK3, and ALK6

Preference	Interactions that promote binding to preferred GF	References
ActRII and ActRIIB bind activins 100- to 1000-fold more avidly than BMPs and GDFs	Intramolecular salt bridge between Lys102 and Asp104 on finger 4 of activin A promotes hydrophobic and H-bond interactions with ActRIIB; ion pairs of Glu111 and Arg87 of activin A with Lys37 and Asp62 of ActRIIB	Thompson et al. 2003; Allendorph et al. 2007; Weber et al. 2007
BMPRII binds BMPs and GDFs, but does not bind activins	BMPRII Tyr113 promotes binding to BMP-2, BMP-7, and GDF-5, but inhibits binding to activin A	Greenwald et al. 2003; Yin et al. 2008
ALK6 binds GDF-5 10- to 20-fold more avidly than ALK3	Rotation of ALK6 by about 9° brings its β1-β2 loop close to Arg57, which protrudes from the pre-helical loop of GDF-5; the equivalent loop of ALK3 has a different conformation that cannot accommodate Arg57	Keller et al. 2004; Kotzsch et al. 2009

GDF, Growth differentiation factor; BMP, bone morphogenetic protein.