title: Structure-function relationship of CAP-Gly domains.
abstract: 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.
authors.affiliation: Biomolecular Research, Structural Biology, Paul Scherrer Insititut, CH-5232 Villigen PSI, Switzerland.
authors.forename: Anke
authors.initials: A
authors.lastname: Weisbrich
authors.forename: Srinivas
authors.initials: S
authors.lastname: Honnappa
authors.forename: Rolf
authors.initials: R
authors.lastname: Jaussi
authors.forename: Oksana
authors.initials: O
authors.lastname: Okhrimenko
authors.forename: Daniel
authors.initials: D
authors.lastname: Frey
authors.forename: Ilian
authors.initials: I
authors.lastname: Jelesarov
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D000072159:Dynactin Complex; D004398:Dyneins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship