# Cihan Atmaca - "The HIV-1 Capsid"

In this study, cofactors and ligands that interact with the HIV capsid are defined.
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**Structure of HIV Capsid**


***Figure 1:** HIV-1 capsid has hexamer structure.*

According to the new studies, this capside interacts with;

* Nuclear pore
* cargo proteins (Nup153, Nup358)
* CPSF6
* Cyclophillin A
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**Domains**
HIV capsid contain two main sides which are comprised of monomers.They are N- terminal domain (NTD) and C- terminal domain (CTD)

***Figure 2:** Domains of capsid*
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**1. Cyclophillin A (CypA)**


***Figure 3:** Binding of CypA with P90 and R55 residues.*

* It is a chaperone
* CypA binds to the CypA-loop which is in the NTD
* CypA specifically binds to a glycine–proline (GP) motif at the centre of this loop
* Maximum three CypA molecules can bind per a hexamer

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**2. CPSF6**


***Figure 4:** Binding of CPSF6 with N57 and N74 residues.*
* It is a cleavage and polyadenylation splicing factor
* A cut region of CPSF6 can limit the HIV infection
* The truncated CPSF6 blocks HIV infection before nuclear entry but after reverse transcription

To give details;

***Figure 5:***
* *CPSF6 and Nup153 cofactors share the same interface of capsid, but the conformation of each cofactor epitope is different and each makes unique interactions with the capsid*
* *Second panel shows that binding of both protein and pharmacological ligands (BI-2 and PF74). All four ligands contain a phenyl ring that superposes exactly.*
* *In the last panel, Only binding of small molecules is mentioned*
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**3.Nup153**

* *It is a core component of the nuclear pore and forms a gel-like matrix that controls transport into the nucleus*
* *This matrix is formed by the C-terminus of Nup153, which contains many phenylalanine-glycine (FG) motif repeats*
* *N74D can prevent the interaction between capsid and CPSF6 but it cannot prevent the interaction between Nup153 and capsid*
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**4. HIV Capsids Are Semi-permeable with an Electrostatic Pore**

* Center of each capsid hexamer has dynamic electrostatic pore
* It was discovered that the -hairpin at the N-terminus is dynamic and can occupy at least two states by trapping the hexamer in various conformational states.

***Figure 6:** The hollow hexamers of HIV-1 capsids have a vast chamber that can only be reached when the β-hairpin (green) assumes a ‘open' conformation.*

***Figure 7: **Yellow and blue represent two neighboring capsid monomers, while green represents CypA. Three functional places in the capsid are labeled to show how close they are to one other: The β-hairpin, the CypA-binding loop, and the CPSF6/Nup153 binding site are the three components of the -hairpin.*

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**5.Conclusion**

To summarize, this study shows that HIV capsid can attach with some cofactors or ligands.

The presence of a cofactor at the CypA-binding loop or the CPSF6/Nup153 interface could affect whether the adjacent β-hairpin is open or closed, and therefore whether IP6 is released or dNTPs are recruited.