The mutation that causes human epidermolysis bullosa simplex is in keratin. Whic
ID: 78008 • Letter: T
Question
The mutation that causes human epidermolysis bullosa simplex is in keratin. Which of the three cytoskeletal fibers is keratin found in? _______ What cellular junction between cells is that cytoskeletal fiber connected to in the cells of the epidermal cell layer? ______ Complete this sentence: The mutated keratin causes skin blistering when skin is exposed to normal friction because the epidermal cells __________ when the epidermal cell layer is ___________ The mutation that causes hereditary equine regional dermal asthenia (HERDA) is a G39R mutation in cyclophilin B, an enzyme that isomerizes prolines in the ER. Amino acid side chains can be negatively charged, positively charged, neutral hydrophobic, or neutral hydrophilic. What is the change in the amino acid property that makes this a loss of function mutation? Glycine (Gly, G) is ___________ Arginine (Arg, R) is ___________ At what stage in collagen synthesis does the loss-of-function mutation in cyclophilin B affect collagen, resulting in stretchy, fragile skin that tears easily? Indicate whether each stage of collagen synthesis is normal (N) or abnormal (A). After an abnormal stage, all downstream stages will be abnormal. single procollagen molecule _________ triple procollagen molecule ________ collagen fibrils _________ collagen fiber _________ The loss-of-function mutations that cause Ehlers-Danlos type VIIC/dermatosparaxis are in procollagen I N-proteinase. At what stage in collagen synthesis does the loss-of-function mutation in procollagen I N-proteinase collagen, resulting in stretchy, fragile skin that tears easily? Indicate whether each stage of collagen synthesis is normal (N) or abnormal (A). After an abnormal stage, all downstream stages will be abnormal. single procollagen molecule __________ triple procollagen molecule _________ collagen fibrils _________ collagen fiber __________ The mutation that causes equine Herlitz-junctional epid bullosa is in the laminin LAMC2, assembled into a trimer with LAMA and LAMB. If the C-terminally truncated mutant LAMC2 assembles into a laminin heterotrimer with LAMA and LAMB, is that laminin trimer functional? __________Explanation / Answer
(I) intermediate filaments
(ii) Desmosomes
(iii) are rendered fragile due to a mutation (usually observed to be dominant) in either K5/K14. Thus on normal friction of the skin, fluid filled blisters form on the skin; exposed to normal physical trauma like scratching or rubbing.
(iii)Here glycine at the 39th position is replaced by arginine.Glycine is non polar and the smallest amino acid and thus it can only be the internal amino acid of a collagen helix.The replacement of glycine by polar arginine would make the collagen structure unstable rendering it functionless and causing loss of function mutation.
(iv)single procollagen molecule-abnormal
triple procollagen molecule - abnormal
collagen fibrils- abnormal
collagen fibers- abnormal
(v) single procollagen molecule-normal
triple procollagen molecule- normal
collagen fibrils- abnormal
collagen fibres - normal
(vi)No,the heterotrimer won't be functional as the mutation causes occurence of premature stop codons/signals forthe gamma subunit of laminin 332.