CRYSTAL STRUCTURE OF A COILED COIL DOMAIN OF HUMAN P160ROCK
CRYSTAL STRUCTURE OF A COILED COIL DOMAIN OF HUMAN P160ROCK
批准号:
8169314
负责人:
MICHAEL J ECK
金额:
$4.69万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-04-01 至 2011-03-31
关键词:
ActinsAsthmaBindingCell PolarityCell physiologyCoiled-Coil DomainComputer Retrieval of Information on Scientific Projects DatabaseCytokinesisEukaryotaFilamentFocal AdhesionsFundingGrantHomologous GeneHumanHypertensionInstitutionLightMediatingMicrofilamentsMorphogenesisNeoplasm MetastasisNeuritesPathway interactionsPlayProcessProteinsROCK1 geneResearchResearch PersonnelResourcesRho-associated kinaseRoleSignal TransductionSmooth MuscleSourceStress FibersStructureTumor Cell InvasionUnited States National Institutes of HealthWorkYeastscell motilitydrug developmentrhoyeast protein
中文摘要
这个子项目是众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Formins are multidomain proteins that participate in a wide range of cytoskeletal processes. They are required for cell polarity, cell migration, cytokinesis, and morphogenesis in all eukaryotes. The defining feature of formin proteins is the Formin Homology 2 (FH2) domain, which directly nucleates actin filaments and remains processively associated with the barbed end of the filament as it grows.
To better understand how formins work in specific cellular contexts, we are studying a genetically and biochemically well-validated formin partner protein, the yeast protein Bud6. Bud6 is a key binding partner and regulator of the formin Bni1 in yeast.
We have recently determined the structure of a core domain in Bud6 that binds to Bni1 (unpublished). Bud6 has no known human homologs. However, re-examination of a weak similarity in primary sequence between this region of Bud6 and the mammalian protein ROCK1, in light of the structure, suggests that the sequence similarity is reflective of a shared structural and perhaps functional feature in these two proteins.
ROCK (Rho-associated kinase) is an effector of Rho-dependent signaling to mediate stress fibers and focal adhesion formation. It is also involved in many other cellular processes including smooth muscle contraction, cell migration, and neurite outgrowth. Abnormal activation of the Rho-ROCK pathway plays role in tumor invasion and metastasis, hypertension, and bronchial asthma.
A structural and functional parallel between the actin binding domains of Bud6 and human ROCK1 if proven correct will be a breakthrough finding. Their similar structures can be a target for drug development.
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