Structure of PDB 8gls Chain A

Receptor sequence

>8glsA (length=1179) Species: 9606 (Homo sapiens)

MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLS
EKLEREWDRELASKKNPKLINALRRCFFWRFMFYGIFLYLGEVTKAVQPL
LLGRIIASYDPDNKEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGM
QMRIAMFSLIYKKTLKLSSRVLDKISIGQLVSLLSNNLNKFDEGLALAHF
VWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGLGRMMMKYRDQ
RAGKISERLVITSEMIENIQSVKAYCWEEAMEKMIENLRQTELKLTRKAA
YVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAV
TRQFPWAVQTWYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAF
WEEGFGELFGTPVLKDINFKIERGQLLAVAGSTGAGKTSLLMVIMGELEP
SEGKIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLE
EDISKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGY
LDVLTEKEIFESCVCKLMANKTRILVTSKMEHLKKADKILILHEGSSYFY
GTFSELQNLQTWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLL
GNTPLNNSYAVIITSTSSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITV
SKILHHKMLHSVLQAPMSTLNTLKAGGILNRFSKDIAILDDLLPLTIFDF
IQLLLIVIGAIAVVAVLQPYIFVATVPVIVAFIMLRAYFLQTSQQLKQLE
SEGRSPIFTHLVTSLKGLWTLRAFGRQPYFETLFHKALNLHTANWFLYLS
TLRWFQMRIEMIFVIFFIAVTFISILTTGEGEGRVGIILTLAMNIMSTLQ
WAVNSSIDVDSLMRSVSRVFKFIDMPTEGDIWPSGGQMTVKDLTAKYTEG
GNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRLLNTEGEIQIDGV
SWDSITLQQWRKAFGVIPQKVFIFSGTFRKNLDPYEQWSDQEIWKVADEV
GLRSVIEQFPGKLDFVLVDGGCVLSHGHKQLMCLARSVLSKAKILLLDQP
SAHLDPVTYQIIRRTLKQAFADCTVILCEHRIEAMLECQQFLVIEENKVR
QYDSIQKLLNERSLFRQAISPSDRVKLFP

3D structure

• PDB: 8gls Structure-based discovery of positive and negative CFTR modulators
• Chain: A
• Resolution: 3.8 Å

Interaction with ligand

Site #	Ligand	Ligand chain	Binding residues on receptor (original residue number in PDB)	Binding residues on receptor (residue number reindexed from 1)	Binding affinity
BS01	peptide	A	L34 T1076 K1080 N1083 L1084	L34 T832 K836 N839 L840
BS02	ATP	A	W401 T460 G461 G463 K464 T465 S466 Q493 C1344 V1345 S1347 G1349	W401 T433 G434 G436 K437 T438 S439 Q466 C1072 V1073 S1075 G1077
BS03	ATP	A	I546 T547 S549 G550 G551 Y1219 T1246 G1249 K1250 S1251 T1252 H1402	I519 T520 S522 G523 G524 Y947 T974 G977 K978 S979 T980 H1130
BS04	ZRH	A	L233 F236 F305 S308 A309 F312 G930 F931	L233 F236 F305 S308 A309 F312 G686 F687

Gene Ontology

Molecular Function

• GO:0005254 chloride channel activity
• GO:0005260 intracellularly ATP-gated chloride channel activity
• GO:0005515 protein binding
• GO:0005524 ATP binding
• GO:0015106 bicarbonate transmembrane transporter activity
• GO:0015108 chloride transmembrane transporter activity
• GO:0016853 isomerase activity
• GO:0016887 ATP hydrolysis activity
• GO:0017081 chloride channel regulator activity
• GO:0019869 chloride channel inhibitor activity
• GO:0019899 enzyme binding
• GO:0030165 PDZ domain binding
• GO:0042626 ATPase-coupled transmembrane transporter activity
• GO:0043225 ATPase-coupled inorganic anion transmembrane transporter activity
• GO:0051087 protein-folding chaperone binding
• GO:0071889 14-3-3 protein binding
• GO:0106138 Sec61 translocon complex binding

Biological Process

• GO:0006695 cholesterol biosynthetic process
• GO:0006821 chloride transport
• GO:0006904 vesicle docking involved in exocytosis
• GO:0015701 bicarbonate transport
• GO:0030301 cholesterol transport
• GO:0034220 monoatomic ion transmembrane transport
• GO:0034976 response to endoplasmic reticulum stress
• GO:0035377 transepithelial water transport
• GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
• GO:0045921 positive regulation of exocytosis
• GO:0048240 sperm capacitation
• GO:0050891 multicellular organismal-level water homeostasis
• GO:0051454 intracellular pH elevation
• GO:0051649 establishment of localization in cell
• GO:0055085 transmembrane transport
• GO:0060081 membrane hyperpolarization
• GO:0070175 positive regulation of enamel mineralization
• GO:0071320 cellular response to cAMP
• GO:0097186 amelogenesis
• GO:1902161 positive regulation of cyclic nucleotide-gated ion channel activity
• GO:1902476 chloride transmembrane transport
• GO:1902943 positive regulation of voltage-gated chloride channel activity
• GO:1904322 cellular response to forskolin

Cellular Component

• GO:0005634 nucleus
• GO:0005737 cytoplasm
• GO:0005765 lysosomal membrane
• GO:0005768 endosome
• GO:0005769 early endosome
• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0005829 cytosol
• GO:0005886 plasma membrane
• GO:0009986 cell surface
• GO:0010008 endosome membrane
• GO:0016020 membrane
• GO:0016324 apical plasma membrane
• GO:0030660 Golgi-associated vesicle membrane
• GO:0030669 clathrin-coated endocytic vesicle membrane
• GO:0031901 early endosome membrane
• GO:0032991 protein-containing complex
• GO:0034707 chloride channel complex
• GO:0055037 recycling endosome
• GO:0055038 recycling endosome membrane

External links

• PDB: RCSB:8gls, PDBe:8gls, PDBj:8gls
• PDBsum: 8gls
• UniProt: P13569|CFTR_HUMAN Cystic fibrosis transmembrane conductance regulator (Gene Name=CFTR)