2hl3
Crystal structure of the A49M mutant CAP-Gly domain of human Dynactin-1 (p150-Glued) in complex with human EB1 C-terminal hexapeptide
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| , resolution 2.03Å | |||||||
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| Gene: | DCTN1 (Homo sapiens) | ||||||
| Related: | 2COY, 1TXQ, 2HKN, 2HL3, 2HL5
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
Dynamic microtubule plus-end tracking protein (+TIP) networks are implicated in all functions of microtubules, but the molecular determinants of their interactions are largely unknown. Here, we have explored key binding modes of +TIPs by analyzing the interactions between selected CAP-Gly, EB-like, and carboxy-terminal EEY/F-COO(-) sequence motifs. X-ray crystallography and biophysical binding studies demonstrate that the beta2-beta3 loop of CAP-Gly domains determines EB-like motif binding specificity. They further show how CAP-Gly domains serve as recognition domains for EEY/F-COO(-) motifs, which represent characteristic and functionally important sequence elements in EB, CLIP-170, and alpha-tubulin. Our findings provide a molecular basis for understanding the modular interaction modes between alpha-tubulin, CLIPs, EB proteins, and the dynactin-dynein motor complex and suggest that multiple low-affinity binding sites in different combinations control dynamic +TIP networks at microtubule ends. They further offer insights into the structural consequences of genetic CAP-Gly domain defects found in severe human disorders.
DiseaseDisease
Known disease associated with this structure: Neuropathy, distal hereditary motor, type VIIB OMIM:[601143], Amyotrophic lateral sclerosis, susceptibility to OMIM:[601143]
About this StructureAbout this Structure
2HL3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Key interaction modes of dynamic +TIP networks., Honnappa S, Okhrimenko O, Jaussi R, Jawhari H, Jelesarov I, Winkler FK, Steinmetz MO, Mol Cell. 2006 Sep 1;23(5):663-71. PMID:16949363
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