Nana | Science Surf

CCR5 annotation, including the known delta32 Mutation and the three mutations introduced by He Jiankui. PAM=Protospacer adjacent motif, DSB=putative double strand break.

From the CCR5 sequence we get the following amino acid sequences

>sp|WT.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL

>sp|-32.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPY
IKDSHLGAGPAAACHGHLLLGNPKNSASVSK

>sp|-15.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCS
SQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL

>sp|-4.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFP
YSINSGRISRH

>sp|+1.P51681|CCR5_HUMANC-Cchemokinereceptortype5OS=HomosapiensOX=9606GN=CCR5PE=1SV=1
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPY
KSVSILEEFPDIKDSHLGAGPAAACHGHLLLGNPKNSASVSK

The -15/WT genotype will have both, a normal and a slightly shortened CCR5 giving no HIV protection at all. The -4/+1 genotype may suffer the fate of non-sense mediated decay. Here are the amino acid predictions for each genotype (I reverted to Topcocns as Protter had some problems in generating correct plots).

Wildtype: There are 7 transmembrane alpha helices I to VII, connected by three extracellular loops (ECL1–3) and three intracellular loops (ICL1–3). ECL2, forms a β-hairpin structure (Tan 2013).

Nana -4 genotype has a much shorter predicted amino acid sequence with missing G protein coupling. Resembles delta 32.

Nana +1 genotype is somewhat longer but missing helices VI and VII. No analogue known.

Lulu -15: resembles wild type, however, will be sensitive to allosteric changes by small-molecule CCR5 inhibitors .

From the original AJHG paper, however, also delta 32 carriers may be HIV infected. As there exists also non-CCR5 dependent virus replication, also Nana is at risk of HIV infection when being virus exposed.

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Phenotype of the CRISPR CAS babies

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