Details

Autor(en) / Beteiligte

• Hajizadeh, Nelly R.
• Pieprzyk, Joanna
• Skopintsev, Petr
• Flayhan, Ali
• Svergun, Dmitri I.
• Löw, Christian

Titel

Probing the Architecture of a Multi-PDZ Domain Protein: Structure of PDZK1 in Solution

Ist Teil von

• Structure (London), 2018-11, Vol.26 (11), p.1522-1533.e5

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The scaffolding protein PDZK1 has been associated with the regulation of membrane transporters. It contains four conserved PDZ domains, which typically recognize a 3–5-residue long motif at the C terminus of the binding partner. The atomic structures of the individual domains are available but their spatial arrangement in the full-length context influencing the binding properties remained elusive. Here we report a systematic study of full-length PDZK1 and deletion constructs using small-angle X-ray scattering, complemented with biochemical and functional studies on PDZK1 binding to known membrane protein partners. A hybrid modeling approach utilizing multiple scattering datasets yielded a well-defined, extended, asymmetric L-shaped domain organization of PDZK1 in contrast to a flexible “beads-on-string” model predicted by bioinformatics analysis. The linker regions of PDZK1 appear to play a central role in the arrangement of the four domains underlying the importance of studying scaffolding proteins in their full-length context. [Display omitted] •PDZK1 has a defined, extended, and L-shaped conformation in solution•The non-PDZ regions of PDZK1 play a key role in supporting a defined conformation•The fourth PDZ domain of PDZK1 also binds to the C terminus of PEPT2•PDZK1 does not adapt a ring-shaped conformation in solution Hajizadeh et al. have performed a systematic study using small-angle X-ray scattering experiments to determine a solution structure of the scaffolding protein PDZK1. The investigation highlights that the four PDZ domains of PDZK1 have a defined L-shaped conformation, which is supported by its linker regions.