2hkn
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Dynamic microtubule plus-end tracking protein (+TIP) networks are | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Honnappa, S.]] | [[Category: Honnappa, S.]] | ||
| - | [[Category: Steinmetz, M | + | [[Category: Steinmetz, M O.]] |
| - | [[Category: Winkler, F | + | [[Category: Winkler, F K.]] |
[[Category: cytoskeleton associated protein]] | [[Category: cytoskeleton associated protein]] | ||
[[Category: eb1 and clip-170 binding protein]] | [[Category: eb1 and clip-170 binding protein]] | ||
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[[Category: strand swap]] | [[Category: strand swap]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:42:51 2008'' |
Revision as of 15:43, 21 February 2008
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Crystal structure of the CAP-Gly domain of human Dynactin-1 (p150-Glued)
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Amyotrophic lateral sclerosis, susceptibility to OMIM:[601143], Neuropathy, distal hereditary motor, type VIIB OMIM:[601143]
About this Structure
2HKN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:42:51 2008
