2pzo

From Proteopedia

Crystal structure of the zinc-knuckle 2 domain of human CLIP-170 in complex with CAP-Gly domain of human Dynactin-1 (p150-Glued)

Overview

In all eukaryotes, CAP-Gly proteins control important cellular processes. The molecular mechanisms underlying the functions of CAP-Gly domains, however, are still poorly understood. Here we use the complex formed between the CAP-Gly domain of p150(glued) and the C-terminal zinc knuckle of CLIP170 as a model system to explore the structure-function relationship of CAP-Gly-mediated protein interactions. We demonstrate that the conserved GKNDG motif of CAP-Gly domains is responsible for targeting to the C-terminal EEY/F sequence motifs of CLIP170, EB proteins and microtubules. The CAP-Gly-EEY/F interaction is essential for the recruitment of the dynactin complex by CLIP170 and for activation of CLIP170. Our findings define the molecular basis of CAP-Gly domain function, including the tubulin detyrosination-tyrosination cycle. They further establish fundamental roles for the interaction between CAP-Gly proteins and C-terminal EEY/F sequence motifs in regulating complex and dynamic cellular processes.

Disease

Known disease associated with this structure: Neuropathy, distal hereditary motor, type VIIB OMIM:[601143], Amyotrophic lateral sclerosis, susceptibility to OMIM:[601143]

About this Structure

2PZO is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure-function relationship of CAP-Gly domains., Weisbrich A, Honnappa S, Jaussi R, Okhrimenko O, Frey D, Jelesarov I, Akhmanova A, Steinmetz MO, Nat Struct Mol Biol. 2007 Oct;14(10):959-67. Epub 2007 Sep 9. PMID:17828277

Page seeded by OCA on Mon Mar 31 04:42:46 2008