Not all genes code for proteins. Provide three examples of RNA’s that do not code for proteins.3ʹ′"3ʹ′"5ʹ′"5ʹ′"U"U"A"A"C"G"Met"GTP"GDP"Ini1ator"tRNA"mRNA"5ʹ′"3ʹ′"Start"codon"mRNA"binding"site"Small"ribosomal"subunit"5ʹ′"P"site"Transla1on"ini1a1on"complex"3ʹ′"E" A"Met"Large"ribosomal"subunit"The Initiation of Translation - Small ribosomal subunit binds to mRNA and scans it for the start codon, AUG - Initiator tRNA binds to the start codon - Large ribosome subunit bindsFig.%17(18(4%Amino%end%of%polypep5de%mRNA"5ʹ′"3ʹ′"E"P"site"A"site"GTP"GDP"E"P"A"E"P" A"GDP"GTP"E"P"A"The"Elonga1on"stage"of"Transla1on"1.%Codon%recogni5on%2.%Pep5de%bond%forma5on%3.%Transloca5on%Release"factor"3ʹ′"5ʹ′"Stop"codon"(UAG,"UAA,"or"UGA)"5ʹ′"3ʹ′"2"Free"polypep1de"2"GDP"GTP"5ʹ′"3ʹ′"Termination of Translation -Release factor protein binds to a Stop codon -Water molecule is added to the C-terminus of the polypeptide chain, breaking the bond between tRNA and polypeptide - Ribosome disassociates from mRNAFig.%17(20%Growing"polypep1des"Completed"polypep1de"Start"of"mRNA"(5ʹ′"end)"Polyribosome"End"of"mRNA"(3ʹ′"end)"(a)"Ribosomes"mRNA"(b)"0.1"µm"Multiple ribosomes can be synthesizing proteins from the same mRNA On average, it takes a ribosome less than a minute to synthesize one proteinFig.%17(21%Ribosome"mRNA"Signal"pep1de"SignalQ"recogni1on"par1cle"(SRP)"CYTOSOL"Transloca1on"complex"SRP"receptor"protein"ER"LUMEN"Signal"pep1de"removed"ER"membrane"Protein"Synthesis of proteins in the Rough ERFig.%5(22%Primary"structure!Secondary"and"ter1ary"structures!Quaternary"structure!Normal"hemoglobin"(top"view)!Primary"structure!Secondary"and"ter1ary"structures!Quaternary"structure!Func1on!Func1on!!"subunit!Molecules"do"not"associate"with"one"another;"each"carries"oxygen.!Red"blood"cell"shape!Normal"red"blood"cells"are"full"of"individual"hemoglobin"moledules,"each"carrying"oxygen.!10"µm!Normal"hemoglobin!!!!!!!!!1! 2! 3! 4! 5! 6! 7!Val!His!Leu!Thr!Pro!Glu!Glu!Red"blood"cell"shape!!"subunit!Exposed"hydrophobic"region!SickleQcell"hemoglobin!!!!!Molecules"interact"with"one"another"and"crystallize"into"a"fiber;"capacity"to"carry"oxygen"is"greatly"reduced.!!!!!Fibers"of"abnormal"hemoglobin"deform"red"blood"cell"into"sickle"shape.!10"µm!SickleQcell"hemoglobin!Glu!Pro!Thr!Leu!His!Val!Val!1! 2! 3! 4! 5! 6! 7!Newly"synthesized"proteins"fold"into"their"3QD"conforma1on"Fig.%5(24"Hollow"cylinder!Cap!Chaperonin"(fully"assembled)!Polypep1de!Steps"of"Chaperonin"Ac1on:!An"unfolded"polyQ"pep1de"enters"the"cylinder"from"one"end.!1!2! 3!The"cap"a`aches,"causing"the"cylinder"to"change"shape"in"such"a"way"that"it"creates"a"hydrophilic"environment"for"the"folding"of"the"polypep1de.!The"cap"comes"off,"and"the"properly"folded"protein"is"released.!Correctly"folded"protein!Chaperonins: protein complexes that assist incorrectly folded protein to refoldFig.%18(12%Proteasome"and"ubiqui1n"to"be"recycled"Proteasome"Protein"fragments"(pep1des)"Protein"entering"a"proteasome"Ubiqui1nated"protein"Protein"to"be"degraded"Ubiqui1n"If a protein can’t refold properly, it is marked by attachment of small ubiquitin proteins and destroyed in ProteasomesAnimation: transcription and translation in real time • http://www.youtube.com/watch?v=41_Ne5mS2lsFig.%17(22%WildQtype"hemoglobin"DNA"mRNA"Mutant"hemoglobin"DNA"mRNA"3ʹ′"3ʹ′"3ʹ′"3ʹ′"3ʹ′"3ʹ′"5ʹ′"5ʹ′"5ʹ′"5ʹ′"5ʹ′"5ʹ′"C" C"T" T"T"T"G"G"A"A"A"A"A" A"A"G"G"U"Normal"hemoglobin" SickleQcell"hemoglobin"Glu"Val"Mutations are changes in the genetic material that can lead to the production of an abnormal protein A"point"muta1on,"change"in"one"base"pair"Substitutions - a type of point mutations A base-pair substitution replaces one nucleotide and its partner with another pair of nucleotides Types of base-pair substitutions: • Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code • Missense mutations still code for an amino acid, but not the right amino acid • Nonsense mutations change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsFig.%17(23a%Wild"type"3ʹ′"DNA"template"strand"3ʹ′"3ʹ′"5ʹ′"5ʹ′"5ʹ′"mRNA"Protein"Amino"end"Stop"Carboxyl"end"A"instead"of"G"3ʹ′"3ʹ′"3ʹ′"U"instead"of"C"5ʹ′"5ʹ′"5ʹ′"Stop"Silent"(no"effect"on"amino"acid"sequence)"Muta1on"in"the"gene"Fig.%17(23b%Wild"type"DNA"template"strand"3ʹ′"5ʹ′"mRNA"Protein"5ʹ′"Amino"end"Stop"Carboxyl"end"5ʹ′"3ʹ′"3ʹ′"T"instead"of"C"A"instead"of"G"3ʹ′"3ʹ′"3ʹ′"5ʹ′"5ʹ′"5ʹ′"Stop"Missense"muta1on"Fig.%17(23c%Wild"type"DNA"template"strand"3ʹ′"5ʹ′"mRNA"Protein"5ʹ′"Amino"end"Stop"Carboxyl"end"5ʹ′"3ʹ′"3ʹ′"A"instead"of"T"U"instead"of"A"3ʹ′"3ʹ′"3ʹ′"5ʹ′"5ʹ′"5ʹ′"Stop"Nonsense"muta1on"Fig.%17(23e%Wild"type"DNA"template"strand"3ʹ′"5ʹ′"mRNA"Protein"5ʹ′"Amino"end"Stop"Carboxyl"end"5ʹ′"3ʹ′"3ʹ′"missing"missing"3ʹ′"3ʹ′"3ʹ′"5ʹ′"5ʹ′"5ʹ′"Frameshid"causing"extensive"missense"(1"baseQpair"dele1on)"• Each of the following options is a modification of the sentence THECATATETHERAT. Which of the following is analogous to a frameshift mutation? A) THERATATETHECAT B) THETACATETHERAT C) THECATARETHERAT D) THECATATTHERAT E) CATATETHERAT• Which of the following DNA mutations is the most likely to be damaging to the function of the protein it specifies? • A) a base-pair deletion • B) a codon substitution • C) a substitution in the last base of a codon • D) a codon deletion • E) a point