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Chapter 4: Functions of Proteins

1. OVERVIEW

  1. This chapter focuses on general concepts of protein function to lay groundwork for all of the metabolism pathways coming up

  2. There are some topics important for Step 1 that we focus on here

    1. Enzyme kinetics

    2. Muscle contraction

    3. Diseases: Marfan's syndrome, cystic fibrosis

  3. Try to group proteins into the ones that do something (i.e., enzymes) and the ones that don't do much (e.g., structural proteins)

  4. Learning about basics of protein function and nomenclature can help you make educated guesses on difficult questions

Structural Proteins

  1. Some important diseases arise from defects in structural proteins, as opposed to proteins that carry out more active functions

2. CYTOSKELETAL PROTEINS

  1. Intracellular structure and cell motility

  2. Microtubules (MTs): In cytosol and cilia — movement of specific things inside the cell

    1. Tubulin heterodimers form the basic structure

    2. Kinesin and dynein are motor proteins that “walk” along MTs

  3. Actin: Cell structure (microfilaments), microvilli, and scaffold for myosin

    1. Actin fibrils are the major structural component of muscles and enable contraction

  4. Intermediate filaments: Varied, used in histopathology to identify cell types

  5. Antimicrobial and anticancer drugs target MTs as “active” in these cell types

    1. Vincristine and vinblastine inhibit MT formation to prevent mitosis of cancer cells

    2. Paclitaxel “locks” MTs in mitosis so cancer cells can't complete division

    3. Colchicine affects neutrophil motility (important for gout)

    4. Mebendazole and griseofulvin affect MT formation in parasites and fungi

  6. Microtubule defects lead to developmental disorders

    1. Kartagener syndrome: Cilia are dysfunctional because of MT motor protein → developmental, reproductive, respiratory problems

Table 4-1.Intermediate filament stains (review).
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Table 4-1. Intermediate filament stains (review).
Stain Cell type Used to identify
Cytokeratin Epithelium Epithelial tissue, e.g., skin, GI, ovarian, squamous cell carcinoma
Desmin Muscle Rhabdomyosarcoma, etc.
Vimentin Mesenchymal tissue Sarcomas, endometrial carcinoma, renal cell carcinoma, meningioma
Neurofilament Neurons Neuroblastoma
Glial fibrillary acidic protein (GFAP) Glia (astrocytes) Astrocytoma, glioblastoma
Figure 4-1.

Cytoskeletal proteins.

An illustration shows the structure of cytoskeletal proteins in multiple forms. An oval-shaped cell is shown, with the top of the cell including a mesh of straight, short microfilaments. Below this are two long and two short microtubules arranged in the form of a cross mark, with the longer tubules in the top and the short ones at the bottom. At the center of these four microtubules are two short cylindrical tube-like structures arranged diagonally to each other. To the left of the larger microtubules is another circular structure with an unevenly coiled chain. To the right of the shorter microtubules and toward the base of the cell is a longer cylinder placed diagonally close to the cell membrane. The inner portion of the cylinder is shown to have a collection of many parallel lines. The cylinder also has two bright-colored rings one each toward the top quarter and bottom quarter of the cylinder. At the membrane toward the outside of the cell, near this cylinder, are about seven tiny spikes. At the bottom left side of the membrane are five larger curved spikes. The caption reads, “cytoskeletal proteins"
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Figure 4-2.

Anti-microtubule drugs.

A set of four illustrations show how different anti-microtubule drugs function. The top left shows vincristine, vinblastine, and paclitaxel acting on a cell, which has two vertical columns of eight multiply colored chromosomes arranged in the center. The four chromosomes on the left are attached to one microtubule chain each. All the four microtubule chains are shown to almost converge on the left end of the cell. At this point are two small cylinders arranged diagonally to each other. A rectangular boxed labeled vincristine and vinblastine is shown outside the cell at the top left position. To the right of the four chromosomes present in the right side are microtubules, but these are not present in an organized manner. These are broken and the individual spheres are strewn around. This too ends in the right side with two small cylindrical structures. In the illustration on the top right is a spherical structure with three horizontal, tube-like extensions to the right. To the left of the sphere portion of the structure are three almost rectangular, yet irregular, structures, small in size and connected to each other. Toward the center of the spherical portion are two small cylindrical structures placed diagonally to each other. around this structure are seven microtubule chains. Four of these chains are short and present within the spherical region, but three of these chains are long and extend all the way through the horizontal extensions of the cell. A label that says colchicine is shown right above the top and middle horizontal extension regions of the cell structure. The bottom left illustration shows a parasite-like worm with a textbox that says mebendazole inside it. The bottom right shows to fungi-like structures with spores attached to each other. A textbox around it is labeled griseofulvin. The caption reads, “anti-microtubule drugs.”
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3. EXTRACELLULAR MATRIX

  1. Extracellular space: Provides scaffold to support connective tissue and skin

  2. Collagen is a key component (reviewed in Chapter 3)

  3. Elastin: Springy substance in organs that need to stretch

    1. Like collagen, has glycine, proline, lysine

    2. Also like collagen, crosslinking of fibers requires lysyl oxidase

      • Inhibition of lysyl oxidase can cause aortic weakness (mimicking Marfan's syndrome)

    3. Differs from collagen on a biochemical level: No hydroxylation

  4. Fibrillin: Another elastic protein that complexes with elastin to provide stretch

  5. α1-antitrypsin deficiency is due to excessive breakdown of elastin because of overactive elastase → emphysema

    1. Lungs primarily affected: Panacinar emphysema

    2. Liver also affected: Site of α1-antitrypsin synthesis

      • Liver is damaged due to accumulation of misfolded protein

  6. Marfan's ...

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