The HIV-1 capsid protein (CA) makes an essential interaction with the human peptidyl prolyl isomerase, cyclophilin A (CypA), that results in packaging of CypA into the virion at a CA to CypA stoichiometry of approximately 10:1. The 231 amino acid residue capsid protein is composed of an amino-terminal CypA binding domain (1 to approximately 151; CA151) and a carboxyl-terminal dimerization domain (approximately 151 to 231). We find that CypA binds dimeric CA and monomeric CA151 with identical intrinsic affinities (K[d] = 16(+/-4) microM). This result demonstrates that capsid dimerization and cyclophilin A binding are not thermodynamically coupled and suggests that the substoichiometric ratio of CypA in the HIV-1 virion results from the intrinsic stability of the CA/CypA complex. In the known co-crystal structure of the CA151/CypA complex, CypA binding is mediated exclusively by an exposed capsid loop that spans residues Pro85 to Pro93. The energetic contributions to CypA binding were quantified for each residue in this loop, and the results demonstrate that the Gly89-Pro90 dipeptide is the primary cyclophilin A recognition motif, with Pro85, Val86, His87, Ala88, and Pro93 also making energetically favorable contacts. These studies reveal that the active site of CypA, which can catalyze the isomerization of proline residues in vitro, also functions as a sequence-specific, protein-binding motif in HIV-1 replication.
ID: AXsUwn94
Submitter: Shu-Ching Ou
Submission Date: Feb. 22, 2019, 12:13 p.m.
Version: 1
Two sets of ΔΔG values are reported. One is from direct calculations using relative Kd, and the other set is reported from the AB-Bind article (DOI: 10.1002/pro.2829)
Number of data points | 84 |
Proteins | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein |
Unique complexes | 17 |
Assays/Quantities/Protocols | Experimental Assay: Kd ; Derived Quantity: ΔΔG_AB-Bind ; Derived Quantity: ΔΔG ; Derived Quantity: Fold decrease in Kd ; Derived Quantity: SD of Kd |
Libraries | Variants for CypA-CA |
Colors: | D | E | R | H | K | S | T | N | Q | A | V | I | L | M | F | Y | W | C | G | P |
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Percent Identity | Matching Chains | Protein | Accession | Entry Name |
---|---|---|---|---|
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P62938 | PPIA_CHLAE |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q0ZQL0 | PPIA_GORGO |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P62937 | PPIA_HUMAN |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q0ZQK8 | PPIA_HYLLA |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P62940 | PPIA_MACMU |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q0ZQK7 | PPIA_NOMLE |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q0ZQL2 | PPIA_PANPA |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q0ZQL1 | PPIA_PANTR |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P62941 | PPIA_PAPAN |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q5R8S7 | PPIA_PONPY |
200.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q0ZQK6 | PPIA_SYMSY |
197.6 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P62935 | PPIA_BOVIN |
197.6 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P62936 | PPIA_PIG |
197.6 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q6DTV9 | PPIA_AOTTR |
197.6 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q0ZQK3 | PPIA_SAGOE |
194.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q8HXS3 | PPIA_FELCA |
194.0 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P14851 | PPIA_CRIGR |
192.6 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9TTC6 | PPIA_RABIT |
192.6 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P17742 | PPIA_MOUSE |
192.6 | A,B | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P10111 | PPIA_RAT |
200.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P12493 | GAG_HV1N5 |
200.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P12497 | POL_HV1N5 |
198.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P05890 | GAG_HV1RH |
198.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P05889 | GAG_HV1W2 |
198.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P35962 | GAG_HV1Y2 |
198.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P05959 | POL_HV1RH |
198.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P35963 | POL_HV1Y2 |
197.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P20873 | GAG_HV1JR |
197.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P20875 | POL_HV1JR |
197.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P03349 | GAG_HV1A2 |
197.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P03369 | POL_HV1A2 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P03347 | GAG_HV1B1 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04593 | GAG_HV1B5 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P03348 | GAG_HV1BR |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04591 | GAG_HV1H2 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q70622 | GAG_HV1LW |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P03366 | POL_HV1B1 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04587 | POL_HV1B5 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P03367 | POL_HV1BR |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04585 | POL_HV1H2 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P0C6F2 | POL_HV1LW |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P05888 | GAG_HV1MN |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P20889 | GAG_HV1OY |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P20892 | POL_HV1OY |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P05887 | GAG_HV1C4 |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P12495 | GAG_HV1Z2 |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P05960 | POL_HV1C4 |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P05961 | POL_HV1MN |
195.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P12499 | POL_HV1Z2 |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q73367 | GAG_HV1B9 |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q73368 | POL_HV1B9 |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04592 | GAG_HV1EL |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04589 | POL_HV1EL |
193.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P18800 | GAG_HV1ND |
193.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P18802 | POL_HV1ND |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P12494 | GAG_HV1J3 |
194.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P12498 | POL_HV1J3 |
189.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9WC53 | GAG_HV1S2 |
189.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9WC54 | POL_HV1S2 |
189.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QBZ6 | GAG_HV1MP |
189.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QBZ5 | POL_HV1MP |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QBY4 | GAG_HV196 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QBZ2 | GAG_HV1M2 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QBY3 | POL_HV196 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QBZ1 | POL_HV1M2 |
186.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9WC62 | GAG_HV1S9 |
186.2 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9WC63 | POL_HV1S9 |
189.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9Q721 | GAG_HV1V9 |
189.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9Q720 | POL_HV1V9 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O12157 | GAG_HV192 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O12158 | POL_HV192 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QC00 | GAG_HV197 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QBZ9 | POL_HV197 |
184.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q75001 | GAG_HV1ET |
184.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04594 | GAG_HV1MA |
184.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q75002 | POL_HV1ET |
184.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P04588 | POL_HV1MA |
184.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QSR4 | GAG_HV1VI |
184.8 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q9QSR3 | POL_HV1VI |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O93182 | GAG_HV190 |
187.6 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O93215 | POL_HV190 |
183.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q1A268 | GAG_SIVMB |
183.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | Q1A267 | POL_SIVMB |
183.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O89291 | GAG_HV193 |
183.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O89290 | POL_HV193 |
183.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P24736 | GAG_HV1U4 |
183.4 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P24740 | POL_HV1U4 |
182.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | P0C1K7 | GAG_HV19N |
182.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O89939 | GAG_HV1SE |
182.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O41798 | POL_HV19N |
182.0 | C,D | Peptidyl-prolyl cis-trans isomerase A,Gag-Pol polyprotein | O89940 | POL_HV1SE |