2HL3

Crystal structure of the A49M mutant CAP-Gly domain of human Dynactin-1 (p150-Glued) in complex with human EB1 C-terminal hexapeptide

Summary for 2HL3

• Entry DOI: 10.2210/pdb2hl3/pdb
• Related: 1TXQ 2COY 2HKN 2HL3 2HL5
• Descriptor: Dynactin-1, Microtubule-associated protein RP/EB family member 1 (3 entities in total)
• Functional Keywords: microtubule binding, dynactin, cytoskeleton associated protein, p150glued, eb1, +tip protein complex structure, eey/f-coo- sequence motif, clip-170, alpha-tubulin, structural protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : Q14203; Cytoplasm, cytoskeleton: Q15691
• Total number of polymer chains: 3
• Total formula weight: 21564.84

Authors

Honnappa, S.,Winkler, F.K.,Steinmetz, M.O. (deposition date: 2006-07-06, release date: 2006-09-12, Last modification date: 2024-02-14)

Primary citation

Honnappa, S.,Okhrimenko, O.,Jaussi, R.,Jawhari, H.,Jelesarov, I.,Winkler, F.K.,Steinmetz, M.O.
Key interaction modes of dynamic +TIP networks.
Mol.Cell, 23:663-671, 2006

PubMed Abstract: 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.

PubMed: 16949363
DOI: 10.1016/j.molcel.2006.07.013

Experimental method

X-RAY DIFFRACTION (2.03 Å)