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Related Concept Videos

Protein Families02:47

Protein Families

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Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism.   Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members.   If these new proteins contain similar amino acids in key...
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Gene Families01:57

Gene Families

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Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
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Distinctive Features of Adult Stem Cells vs Cancer Stem Cells01:18

Distinctive Features of Adult Stem Cells vs Cancer Stem Cells

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A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells.
Adult stem cells
Adult stem cells are tissue-specific; hence, they divide to develop the tissue from which they originate. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of the skin. Adult bone marrow has three distinct types of stem cells:...
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Structural Protein Function01:56

Structural Protein Function

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Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
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Structural Protein Function

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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.

Peter Canning1, Kwangjin Park2, João Gonçalves3

  • 1Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.

Cell Reports
|February 9, 2018
PubMed
Summary
This summary is machine-generated.

Cyclin-dependent kinase-like (CDKL) proteins regulate primary cilia. Structural and functional studies reveal CDKLs

Keywords:
CDKLCyclin-Dependent Kinase-Likecilium lengthkinaseneurological disorderprotein structure

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Neuroscience

Background:

  • Primary cilia are crucial for signaling and development, with their growth regulated by kinases like cyclin-dependent kinases (CDKs).
  • Neurological disorders associated with CDK-Like (CDKL) proteins suggest their involvement in similar cellular processes.

Purpose of the Study:

  • To elucidate the structure and function of human CDKL proteins.
  • To investigate the role of CDKLs in primary cilia and their connection to neurological disorders.

Main Methods:

  • Determined crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5.
  • Analyzed evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs).
  • Investigated the function of Caenorhabditis elegans CDKL-1 and human CDKL5 in cilia.

Main Results:

  • Revealed evolutionary divergence of CDKLs from CDKs and MAPKs, highlighting an unusual ?J helix critical for CDKL2 and CDKL3 activity.
  • C. elegans CDKL-1, localized to neuronal cilia, modulates cilium length via kinase activity and its C-terminal ?J helix.
  • Human CDKL5 localizes to cilia and impairs ciliogenesis upon overexpression; patient mutations in CDKL5 cause cilia defects.

Conclusions:

  • CDKLs possess unique structural features, including the ?J helix, differentiating them from CDKs and MAPKs.
  • CDKLs, particularly CDKL5, play a role in cilia function, and defects in this process may underlie neurological disorders like epilepsy.
  • Established a disease model linking cilium length defects to neurological conditions, offering insights into pathogenesis.