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Identities of P2 and P3 Residues of H-2Kb-Bound Peptides Determine Mouse Ly49C Recognition.

Marquez EA, Kane KP - PLoS ONE (2015)

Bottom Line: Despite this ability, little is understood regarding the properties that enable some peptides, when bound to MHC-I molecules, to support Ly49 recognition, but not others.Using RMA-S target cells expressing MHC-I molecules loaded with individual peptides and effector cells expressing the ectodomain of the inhibitory Ly49C receptor, we found that two adjacent amino acid residues, P2 and P3, both buried in the peptide binding groove of H-2Kb, determine mouse Ly49C specificity.If both are aliphatic residues, this is supportive.

View Article: PubMed Central - PubMed

Affiliation: Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT
Ly49 receptors can be peptide selective in their recognition of MHC-I-peptide complexes, affording them a level of discrimination beyond detecting the presence or absence of specific MHC-I allele products. Despite this ability, little is understood regarding the properties that enable some peptides, when bound to MHC-I molecules, to support Ly49 recognition, but not others. Using RMA-S target cells expressing MHC-I molecules loaded with individual peptides and effector cells expressing the ectodomain of the inhibitory Ly49C receptor, we found that two adjacent amino acid residues, P2 and P3, both buried in the peptide binding groove of H-2Kb, determine mouse Ly49C specificity. If both are aliphatic residues, this is supportive. Whereas, small amino acids at P2 and aromatic amino acids at the P3 auxiliary anchor residue are detrimental to Ly49C recognition. These results resemble those with a rat Ly49 where the identity of a peptide anchor residue determines recognition, suggesting that dependence on specific peptide residues buried in the MHC-I peptide-binding groove may be fundamental to Ly49 peptide selectivity and recognition.

No MeSH data available.


Related in: MedlinePlus

Structural analysis of peptide amino acid docking into the B-pocket of H-2Kb.The H-2Kb bound peptide amino acid at position 2 (P2) docks into the B-pocket of H-2Kb in H-2Kb-RGYVYQGL. Figure shows the H-2Kb-RGYVYQGL heavy chain in gray ribbon, the RGYVYQGL peptide is in teal. The figure was generated using CHIMERA UCSF software and PDB ID 1KPU for H-2Kb-RGYVYQGL.
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pone.0131308.g006: Structural analysis of peptide amino acid docking into the B-pocket of H-2Kb.The H-2Kb bound peptide amino acid at position 2 (P2) docks into the B-pocket of H-2Kb in H-2Kb-RGYVYQGL. Figure shows the H-2Kb-RGYVYQGL heavy chain in gray ribbon, the RGYVYQGL peptide is in teal. The figure was generated using CHIMERA UCSF software and PDB ID 1KPU for H-2Kb-RGYVYQGL.

Mentions: From our experiments, in addition to P3, the P2 residue, that docks into the B-pocket formed by residues Tyr7, Val9, Glu24, Try45 and Asn70, is important in determining Ly49C and H-2Kb binding [34,36]. In the H-2Kb-RGYVYQGL structure, Gly at P2 allows for a water molecule to fill the negatively charged B-pocket of H-2Kb and contribute to an extensive hydrogen bond network that stabilizes the core of the peptide-binding groove [35,36]. In the H-2Kb-RGYVYQGL, this network involves the hydroxyl group of Tyr at P5 in the C-pocket and the α-carbon of P3 and a pseudobond with Glu24 within the B-pocket (Fig 6). On the other hand, with the H-2Kb-SIINFEKL structure, Ile at P2 fully occupies the B-pocket, leaving no space for water molecules, possibly increasing the flexibility of the core of the peptide binding groove and decreasing the free energy requirements for Ly49C binding of H-2Kb.


Identities of P2 and P3 Residues of H-2Kb-Bound Peptides Determine Mouse Ly49C Recognition.

Marquez EA, Kane KP - PLoS ONE (2015)

Structural analysis of peptide amino acid docking into the B-pocket of H-2Kb.The H-2Kb bound peptide amino acid at position 2 (P2) docks into the B-pocket of H-2Kb in H-2Kb-RGYVYQGL. Figure shows the H-2Kb-RGYVYQGL heavy chain in gray ribbon, the RGYVYQGL peptide is in teal. The figure was generated using CHIMERA UCSF software and PDB ID 1KPU for H-2Kb-RGYVYQGL.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493100&req=5

pone.0131308.g006: Structural analysis of peptide amino acid docking into the B-pocket of H-2Kb.The H-2Kb bound peptide amino acid at position 2 (P2) docks into the B-pocket of H-2Kb in H-2Kb-RGYVYQGL. Figure shows the H-2Kb-RGYVYQGL heavy chain in gray ribbon, the RGYVYQGL peptide is in teal. The figure was generated using CHIMERA UCSF software and PDB ID 1KPU for H-2Kb-RGYVYQGL.
Mentions: From our experiments, in addition to P3, the P2 residue, that docks into the B-pocket formed by residues Tyr7, Val9, Glu24, Try45 and Asn70, is important in determining Ly49C and H-2Kb binding [34,36]. In the H-2Kb-RGYVYQGL structure, Gly at P2 allows for a water molecule to fill the negatively charged B-pocket of H-2Kb and contribute to an extensive hydrogen bond network that stabilizes the core of the peptide-binding groove [35,36]. In the H-2Kb-RGYVYQGL, this network involves the hydroxyl group of Tyr at P5 in the C-pocket and the α-carbon of P3 and a pseudobond with Glu24 within the B-pocket (Fig 6). On the other hand, with the H-2Kb-SIINFEKL structure, Ile at P2 fully occupies the B-pocket, leaving no space for water molecules, possibly increasing the flexibility of the core of the peptide binding groove and decreasing the free energy requirements for Ly49C binding of H-2Kb.

Bottom Line: Despite this ability, little is understood regarding the properties that enable some peptides, when bound to MHC-I molecules, to support Ly49 recognition, but not others.Using RMA-S target cells expressing MHC-I molecules loaded with individual peptides and effector cells expressing the ectodomain of the inhibitory Ly49C receptor, we found that two adjacent amino acid residues, P2 and P3, both buried in the peptide binding groove of H-2Kb, determine mouse Ly49C specificity.If both are aliphatic residues, this is supportive.

View Article: PubMed Central - PubMed

Affiliation: Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT
Ly49 receptors can be peptide selective in their recognition of MHC-I-peptide complexes, affording them a level of discrimination beyond detecting the presence or absence of specific MHC-I allele products. Despite this ability, little is understood regarding the properties that enable some peptides, when bound to MHC-I molecules, to support Ly49 recognition, but not others. Using RMA-S target cells expressing MHC-I molecules loaded with individual peptides and effector cells expressing the ectodomain of the inhibitory Ly49C receptor, we found that two adjacent amino acid residues, P2 and P3, both buried in the peptide binding groove of H-2Kb, determine mouse Ly49C specificity. If both are aliphatic residues, this is supportive. Whereas, small amino acids at P2 and aromatic amino acids at the P3 auxiliary anchor residue are detrimental to Ly49C recognition. These results resemble those with a rat Ly49 where the identity of a peptide anchor residue determines recognition, suggesting that dependence on specific peptide residues buried in the MHC-I peptide-binding groove may be fundamental to Ly49 peptide selectivity and recognition.

No MeSH data available.


Related in: MedlinePlus