3RRQ,2M2D,3BIK,3BP6,4ZQK,5B8C,5GGR,5IUS,5JXE,5WT9


Conserved Protein Domain Family
IgV_PD1

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cd16088: IgV_PD1 
Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1)
The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.
Statistics
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PSSM-Id: 409509
Aligned: 16 rows
Threshold Bit Score: 198.885
Created: 21-Apr-2015
Updated: 17-Aug-2020
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 21 residues -Click on image for an interactive view with Cn3D
Feature 1:PD-1/PD-L1 complex [polypeptide binding site]
Evidence:
  • Structure:3BIK: mouse PD1 binds ligand PD-L1, contacts at 4A
  • Comment:PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                    # # #    #### #    ## # # #         
3RRQ_A         3 PPTFSPALLVVTEGDNATFTCSFSnts--------------esFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQ 68  human
3BIK_B        11 SLTFYPAWLTVSEGANATFTCSLSnws--------------edLMLNWNRLSPSNQTEKQAAFSNGLSQPVQDARFQIIQ 76  house mouse
3BP6_A         1 SLTFYPAWLTVSEGANATFTCSLSnws--------------edLMLNWNRLSPSNQTEKQAAFSNGLSQPVQDARFQIIQ 66  house mouse
5B8C_C         5 PPTFSPALLVVTEGDNATFTCSFSnts--------------esFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDSRFRVTQ 70  human
5GGR_Y         9 PPTFSPALLVVTEGDNATFTCSFSnts--------------esFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDSRFRVTQ 74  human
5JXE_A         2 PPTFSPALLVVTEGDNATFTCSFSnts--------------esFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDSRFRVTQ 67  human
ELK14422      37 PLTFNPPQLSVAEGETATFTCSFSnts--------------ehFVLNWYRLSPRNQTDKLAAFPEDGSQPRSNRRFHVTR 102 Pteropus alecto
XP_004695897  73 PPTISPARLSVPEGGNASFTCSLShdalptphdtqpaprdtqqARLNWYRLGPGNQSSKLAAFPEDQHQAGQDWRFRVTP 152 star-nosed mole
NP_001301026  34 PLTFSPAQLTVQEGENATFTCSLAdip--------------dsFVLNWYRLSPRNQTDKLAAFQEDRIEPGRDRRFRVTR 99  Canis lupus fam...
XP_020768864  34 ALTFSPARLVVPEGANATFTCSFSskp--------------ehFVLNWYRMSPSNQTDKLAAFPEDRSQPGRDQRFRVTP 99  Odocoileus virg...
Feature 1                              # #   # ### # #         
3RRQ_A        69 LPNGRDFHMSVVRARRNDSGTYLCGAISLAPKLQIKESLRAELRVT 114 human
3BIK_B        77 LPNRHDFHMNILDTRRNDSGIYLCGAISLHPKAKIEESPGAELVVT 122 house mouse
3BP6_A        67 LPNRHDFHMNILDTRRNDSGIYLCGAISLHPKLKIEESPGAELVVT 112 house mouse
5B8C_C        71 LPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVT 116 human
5GGR_Y        75 LPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVT 120 human
5JXE_A        68 LPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVT 113 human
ELK14422     103 LPNGRDFQMSVLAAQRNDSGTYLCGAISLLPRTQISESPRAELTVT 148 Pteropus alecto
XP_004695897 153 LPGGRDFLLTLVGARPHDSGTYLCVAIYLNPRVHFSESPHIKLTVT 198 star-nosed mole
NP_001301026 100 LPNGRDFHMSIVAARLNDSGIYLCGAIYLPPNTQINESPRAELSVT 145 Canis lupus familiaris
XP_020768864 100 LPDGQHFLMSVVAAQRNDSGVYFCGAIYLPPRTQINESHPAELTVT 145 Odocoileus virginianus texanus

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