The transition state for coupled folding and binding of a disordered DNA binding domain resembles the unbound state.

The basic zippers (bZIPs) are one of two large eukaryotic families of transcription factors whose DNA binding domains are disordered in isolation but fold into stable α-helices upon target DNA binding. Here, we systematically disrupt pre-existing helical propensity within the DNA binding region of the homodimeric bZIP domain of cAMP-response element binding protein (CREB) using Ala-Gly scanning and examine the impact on target binding kinetics. We find that the secondary structure of the transition state strongly resembles that of the unbound state.

Modular design of bi- and multi-specific knob domain fusions.

Introduction: The therapeutic potential of bispecific antibodies is becoming widely recognised, with over a hundred formats already described. For many applications, enhanced tissue penetration is sought, so bispecifics with low molecular weight may offer a route to enhanced potency. Here we report the design of bi- and tri-specific antibody-based constructs with molecular weights as low as 14.

Binding and folding in transcriptional complexes.

Transcription factors are among the classes of proteins with the highest levels of disorder. Investigation of these regulatory proteins is uncovering not just the mechanisms that underlie gene regulation, but relationships that apply to all intrinsically disordered proteins. Recent studies confirm that binding does not necessarily induce folding but that when it does, it tends to follow induced fit mechanisms.

[Expression of sperm-specific glyceraldehyde-3-phosphate dehydrogenase in melanoma cells changes their energy metabolism].

The somatic isoform of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC1.2.1.

Dimerization of Tyr136Cys alpha-synuclein prevents amyloid transformation of wild type alpha-synuclein.

Expression of human alpha-synuclein in E. coli cells is known to result in a mixture of the wild type alpha-synuclein and the protein containing Tyr136Cys substitution due to the translational error. The amount of Cys136 alpha-synuclein (Cys136-AS) may reach approximately 50% of the recombinant protein.