Natural Killer Cell Receptors

Rangarajan, Sampath; Mariuzza, Roy A.

doi:10.1016/b978-0-12-803369-2.00004-8

Cited by 3 publications

(3 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon the formation of a stable peptide-loaded MHC (pMHC), the complex is transported to the cell surface, and presents peptide ligands to immune cell receptors such as the T-Cell Receptor (TCR) of cytotoxic CD8+ T-cells, and Killer-cell Immunoglobulin-like Receptors (KIRs) of Natural Killer (NK) cells [23][24][25][26].…”

Section: Plos Onementioning

confidence: 99%

See 1 more Smart Citation

Sequence-structure-function relationships in class I MHC: A local frustration perspective

Serçinoğlu

Ozbek

2020

PLoS ONE

View full text Add to dashboard Cite

Class I Major Histocompatibility Complex (MHC) binds short antigenic peptides with the help of Peptide Loading Complex (PLC), and presents them to T-cell Receptors (TCRs) of cytotoxic T-cells and Killer-cell Immunglobulin-like Receptors (KIRs) of Natural Killer (NK) cells. With more than 10000 alleles, human MHC (Human Leukocyte Antigen, HLA) is the most polymorphic protein in humans. This allelic diversity provides a wide coverage of peptide sequence space, yet does not affect the three-dimensional structure of the complex. Moreover, TCRs mostly interact with HLA in a common diagonal binding mode, and KIR-HLA interaction is allele-dependent. With the aim of establishing a framework for understanding the relationships between polymorphism (sequence), structure (conserved fold) and function (protein interactions) of the human MHC, we performed here a local frustration analysis on pMHC homology models covering 1436 HLA I alleles. An analysis of local frustration profiles indicated that (1) variations in MHC fold are unlikely due to minimally-frustrated and relatively conserved residues within the HLA peptide-binding groove, (2) high frustration patches on HLA helices are either involved in or near interaction sites of MHC with the TCR, KIR, or tapasin of the PLC, and (3) peptide ligands mainly stabilize the Fpocket of HLA binding groove.

show abstract

Section: Plos Onementioning

confidence: 99%

“…On the other hand, HLA allelic diversity may affect interactions with other proteins as well. Only certain allele groups containing specific epitopes interact with KIR [25,37]. Structural details of the PLC-pMHC interaction were also only recently revealed [34,[38][39][40][41].…”

Section: Plos Onementioning

confidence: 99%

Sequence-structure-function relationships in class I MHC: A local frustration perspective

Serçinoğlu

Ozbek

2020

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…On the other hand, HLA allelic diversity may affect interactions of the pMHC with other proteins as well. Only certain allele groups containing specific epitopes interact with KIR [25,37]. Structural details of the PLC-pMHC interaction were also only recently revealed [34,38–41].…”

Section: Introductionmentioning

confidence: 99%

Sequence-structure-function relationships in class I MHC: a local frustration perspective

Serçinoğlu

Ozbek

2019

Preprint

View full text Add to dashboard Cite

12 Class I Major Histocompatibility Complex (MHC) binds short antigenic peptides with the 13 help of Peptide Loading Complex (PLC), and presents them to T-cell Receptors 14 (TCRs) of cytotoxic T-cells and Killer-cell Immunglobulin-like Receptors (KIRs) of 15 Natural Killer (NK) cells. With more than 10000 alleles, the Human Leukocyte Antigen 16 (HLA) chain of MHC is the most polymorphic protein in humans. This allelic diversity 17 provides a wide coverage of peptide sequence space, yet does not affect the three-18 dimensional structure of the complex. Moreover, TCRs mostly interact with pMHC in a 19 common diagonal binding mode, and KIR-pMHC interaction is allele-dependent. With 20 the aim of establishing a framework for understanding the relationships between 21 polymorphism (sequence), structure (conserved fold) and function (protein interactions) 22 of the MHC, we performed here a local frustration analysis on pMHC homology models 23 covering 1436 HLA I alleles. An analysis of local frustration profiles indicated that (1) 24 variations in MHC fold are unlikely due to minimally-frustrated and relatively conserved 25 residues within the HLA peptide-binding groove, (2) high frustration patches on HLA 26 helices are either involved in or near interaction sites of MHC with the TCR, KIR, or 27 Tapasin of the PLC, and (3) peptide ligands mainly stabilize the F-pocket of HLA 28 binding groove. 29 Author Summary30 A protein complex called the Major Histocompatibility Complex (MHC) plays a critical 31 role in our fight against pathogens via presentation of antigenic peptides to receptor 32 molecules of our immune system cells. Our knowledge on genetics, structure and 33 protein interactions of MHC revealed that the peptide-binding groove of Human 3 34 Leukocyte Chain (HLA I) of this complex is highly polymorphic and interacts with 35 different proteins for peptide-binding and presentation over the course of its lifetime.36 Although the relationship between polymorphism and peptide-binding is well-known, 37 we still lack a proper framework to understand how this polymorphism affects the 38 overall MHC structure and protein interactions. Here, we used computational 39 biophysics methods to generate structural models of 1436 HLA I alleles, and quantified 40 local frustration within the HLA I, which indicates energetic optimization levels of 41 contacts between amino acids. We identified a group of minimally frustrated and 42 conserved positions which may be responsible for the conserved MHC structure, and 43 detected high frustration patches on HLA surface positions taking part in interactions 44 with other immune system proteins. Our results provide a biophysical basis for 45 relationships between sequence, structure, and function of MHC I. 46 4 47 48The sequence-structure-function paradigm plays a central role in structural 49 biology: the primary structure (i.e. amino acid sequence) of a protein dictates the three-50 dimensional structure (fold), which in turn influences the function [1-3]. The close 51 relationship bet...

show abstract