GMEP mutations are broadly distributed throughout VHL and the resulting amino acid changes are predicted to have diverse effects on pVHL and the VCB complex; some, such as F119S, are severely destabilizing hydrophobic core mutations; others, such as D143Q, are minimally destabilizing surface mutations.
In reality, it's a labor war, and it has destabilized the core of what it means to be a professional driver.
Lengthening your gait in this manner stretches out your leg muscles and destabilizes your core, leading to discomfort over time.
Thus, the substitution from aromatic to hydrophilic residue may destabilize the helicase core, and thereby affect the catalytic activity (indeed, F637S exhibited the least helicase and ATPase activity).
Phosphates on activated receptors destabilize that "polar core" and allow binding of specific receptor residues at the fulcrum of, and on the concave faces of, the two arrestin domains.
Many missense mutations that affect this domain of J-1 cause Alagille syndrome, a developmental disorder that is usually associated with J-1 haploinsufficiency, and mapping these mutations onto our structure suggests that they destabilize the hydrophobic core and prevent correct folding of the C2 domain.
The smaller fragments below 15 kDa represent degradation products of the destabilized 25 kDa core domain of ΔF508 NBD1.
We therefore concluded that deletion of F508 destabilizes isolated NBD1 core domain in biological context as has been shown before in vitro [10], [13], [14].
Receptor-attached phosphates destabilize both the polar core (Vishnivetskiy et al., 1999) and three-element interaction (Vishnivetskiy et al., 2000), enabling transition into high-affinity receptor-binding state.
Analysis of the three-dimensional structure showed that substitution of Phe 151 with Leu produces a hydrophobic cavity in the GSTP1 core, thereby destabilizing its structure.
Activating mutations destabilizing inter-domain polar core significantly enhance clathrin and AP2 binding (Milano et al., 2002), likely by increasing overall flexibility of the molecule and the probability of the C-tail release in free arrestins.
