6ezi | pdb_00006ezi
PDZK1 domain 4 in complex with C-terminal peptide of human PepT2.
Structural highlights
Function[NHRF3_HUMAN] A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. May function to connect SCARB1 with the cellular machineries for intracellular cholesterol transport and/or metabolism. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function (By similarity). [S15A2_HUMAN] Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides (PubMed:7756356). Transports the dipeptide-like aminopeptidase inhibitor bestatin (By similarity). Can also transport the aminocephalosporin antibiotic cefadroxil (By similarity).[UniProtKB:P46029][UniProtKB:Q63424][1] Publication Abstract from PubMedThe 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. Probing the Architecture of a Multi-PDZ Domain Protein: Structure of PDZK1 in Solution.,Hajizadeh NR, Pieprzyk J, Skopintsev P, Flayhan A, Svergun DI, Low C Structure. 2018 Aug 16. pii: S0969-2126(18)30262-4. doi:, 10.1016/j.str.2018.07.016. PMID:30220543[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
