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Lecture 3

HMB200 2014 Lecture 3.pdf
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Department
Human Biology
Course
HMB200H1
Professor
John Yeomans
Semester
Winter

Description
  Lecture  3:  Proteins  and  Transmitters     Neurons  and  Proteins   - what  makes  neurons  special?  Proteins   o Proteins  extend  long  ways  out  to  dendrites  and  axons   - anatomy:  structural  proteins,   filaments,  and  fibers   o Structural  proteins  and  filaments  and  fibers  that  give  neuron  their  complex  shape   - axons:  action  potential  due  to  voltage -­‐gated  channels   o Within  axons,  action  potential  result  from  pumps  and  voltage  gated  channels  which  allow  ion  o  be   controlled  by  voltage  gated  and  leakage  channels   - synapses:  hundreds  of  presynaptic  proteins  for  transmitters     o 100s  of  presynaptic  proteins  that  respond  to  transmitter  and   influence  the  release  of  transmitter’s   o complex  processes,  involves  calcium  media ted  synaptic   proteins   o in  the  postsynaptic  side,  there  are  100s  of  proteins  for   responding  to  transmitter  à  for  signaling,  changes  in   postsynaptic  neurons,  as  well  as  for  the  activation  of  gene   transcription  and  growth  in  the  postsynaptic  neuron   o Complexity  of  synaptic  protein:  give  brain  ability  to  create   memories,  growth,  and  thoughts     Chemical  Synapse   - calcium  entry  results  in  the  release  of  chemicals,  action  on   receptors,  and  ultimately  the  EPSP,  and  IPSPs  (which  are   integrated  to  produce  postsynaptic  actions)     Protein  Structure  and  Distribution   - DNA  à mRNA   à  proteins   o mRNA  is  transcribed  from  the  double  helix,  leaves  the  nucleus  into   the  cytoplasm,  and  translated  to  make  proteins  (amino  acids)   - Protein  chains  can  be  read  from  DNA  in  genome   - Side  chains  interact  to  make  3D  structure   o Proteins  can  create  3D  structures  instead  of  a  1  dimensional  chain   (little  flexibility)   o These  long  protein  chains  with  their  side  interacting  molecules  can   then  interact  with  each  other  to  make  complex  3D  structures   - Primary,  secondary,  tertiary  structure   o Complex  3D  structures  that  make  ribosomes  and  histones  in  cell   à   which  can  then  make  enzymes,  receptors,  and  channels  on  surface   of  a  cell  à  which  in  turn,  allows  action  potentials  and  transmitter   actions   o Primary  structure:  initial  chain  of  amino  acids   o Secondary  structure:  involves  interactions  between  the  cysteine   groups  (interacting  side  chains  assemble  the  secondary  structure   from  primary  OR  by  interactions  with  membranes  OR  interactions   between  protein  and  cytoplasm)   o Tertiary  structure:  the  final  structure  of  the  assembled  protein   - Hydrophilic  and  lipophilic  regions:  Lipids  bind  to  membranes   - Trafficking  in  cell  by  tail  code     Voltage-­‐Gated  Na+  Channel  (a  protein)   - Needed  for  action  potentials   - One  single  chain  interacting  with  the  membranes     - Many  of  these  amino  acids  are  lipophilic   à  attracted  to  lipid  membranes   - These  chains  of  amino  acids  then  bind  the  membrane  and  form  transmembrane  loops   à  24  transmembrane  loops  in  voltage  gated  Na+  channel     - Many  other  amino  acids  attract  to  water  (sits  in  the  fluid  part   -­‐  cytosol)  –  hydrophilic         - Transmembrane  protein  is  made  of  lipophilic  and  hydrophilic  loops  (chain  folds  up  to  interact  in  their  respective   favourable  environment)   - Once  transmembrane  loop  is  e stablished,  by  way  of  lipophilic  and  hydrophilic  portions,  they  can  then  combine   with  each  other  to  form  pores  (2D à  3D  structure)   - 3D  structure:  capable  of  having  a  voltage  gated  property     Voltage-­‐Gated  Channels  (how  they  fold  up)   - Bars:  lipophilic  transmem brane  part  of  protein   - lipophilic  portions  surrounds  the  pour  where  ions  flow     Molecules  in  Brain   - there  are  1000s  of  proteins  that  are  expressed  in  the  brain,  so  how  can   we  find  these  proteins?  Which  neurons  are  they  expressed  in?  are  they   membrane  proteins?  Are  they  cytosol  proteins?  Which  enzymes  will  they   interact  with?   à  2  major  methods:  In  order  to  find  mRNA,  take  a  label  chain  that’s   complementary  to  the  RNA  of  interest     - in  situ  hybridization  used  to  find  mRNA  location  in  brain   o You  an  read  where  proteins  are  by  looking  at  the  genome   o To  find  critical  genes:  know  how  genes  are  activated  by  start  codon   à  Find  start  and  stop  location,  then  you  can  find  where  the  genes   will  be  expressed  (by  going  from  the  start  point  to  the  stop  point   à   found  in  the  genome)   o You  can  then  trace  from  start  to  stop  where  the  nucleic  acids  will  be   read  à  each  3  bases  makes  1  amino  acid   o Trinucleotide  code:  3  bases  each   o This  code  is  used  to  read  off  what  proteins  are  going  to  be  made   (what  the  sequence  of  amino  acids  are  going  to  be)   o Once  you  know  sequence  of  DNA,  you  can  read  what  sequence   -­‐  label  probe  (complementary  and  hybridizes  
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