PDZ Structure and Implication in Selective Drug Design against Cystic Fibrosis.

Abstract:

:PDZ domains play an essential role in a number of cellular processes by facilitating protein scaffolding and assembly of protein complexes. These domains consist of 80 to 90 amino acids and are found to recognize short C-terminal sequences of target proteins. Protein complex formation between PDZ target molecules can lead to a number of signaling and regulatory cascades that may either promote or inhibit the activation of certain proteins. It has been shown that the interaction of the PDZ domains of NHERF2 with LPA2 plays an inhibitory role on the cystic fibrosis transmembrane conductance regulator (CFTR) by promoting the assembly of a CFTR-NHERF2-LPA2 complex. CFTR regulates chloride ion transport across the epithelial plasma membrane, and individuals possessing CFTR mutations show decreased protein function and consequently, viscous mucus accumulation due to improper fluid transport. This type of ailment is termed cystic fibrosis. Thus, insight to the structure of PDZ domains and how they function to form macromolecular complexes could be therapeutically important in augmenting CFTR channel activity in cystic fibrosis patients. Here we review the PDZ domain family while dissecting their structure, function and implications in CFTR regulation and cystic fibrosis.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Holcomb J,Spellmon N,Trescott L,Sun F,Li C,Yang Z

doi

10.2174/1389450116666141219120125

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

945-50

issue

9

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-64102

journal_volume

16

pub_type

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