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This page contains a collaboration between User:Eric Martz and the ConSurf Team. Please edit this page only if you are a participant in this collaboration. Thank you.

Functional Loop 220-230 in MHC Alpha ChainFunctional Loop 220-230 in MHC Alpha Chain

In MHC Class I (mouse and human) Q226 is part of the binding site for CD8[1]. Regarding the alpha chain (A) in human MHC 1akj, the authors state:

A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction ....

Hydrogen bonds between CD8 and the alpha chain of HLA-A2 that involve this loop are (from Table 2[1]):

CD8:D  T30.OG1 : T225.O     HLA-A2:A  2.7 Å
CD8:E  S34.OG  : Q226.NE2             3.0
CD8:D  S100.O  : Q226.NE2             3.0
CD8:D  S100.OG : Q226.O               2.7
CD8:E  Y51.OH  : D227.OD2             3.0
CD8:D  N99.OD1 : L230.N               3.0
CD8:D  N99.ND2 : L230.O               3.4
CD8:D  S27.OG1 : E232.OE1             2.7

Similar interactions occur in the mouse in 1bqh[2]. Sequence comparison of the alpha chain of MHC in the CD8-binding regions:

195-198 220-230
HLA-A2 SDHE D GEDQT QDTEL
H-2Kb PEDK N GEELI QDMEL

ConSurf Results for 220-230ConSurf Results for 220-230

2VAA chain A
Server Number of
Sequences
Cons. Grades
220-230
Av. Cons. Gr.
220-230
APD Job Link
ConSurf-DB 144 8 57776 48775 7.1 1.72 consurfdb
ConSurf all=218 8 76565 45553 5.9 1.17 1237248584
ConSurf 150 8 66356 66365 6.0 0.52 1237414642
ConSurf 139 8 98466 98577 7.7 0.36 1237421568
ConSurf 100 8 99688 99899 9.2 0.20 1237327837
ConSurf 70 7 99?88 98799 8.3 0.22 1237327964

? = insufficient data.
APD = Average Pairwise Difference in the Multiple Sequence Alignment.

ReferencesReferences

  1. 1.0 1.1 Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, Bell JI, Jones EY, Jakobsen BK. Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. Nature. 1997 Jun 5;387(6633):630-4. PMID:9177355 doi:http://dx.doi.org/10.1038/42523
  2. Kern PS, Teng MK, Smolyar A, Liu JH, Liu J, Hussey RE, Spoerl R, Chang HC, Reinherz EL, Wang JH. Structural basis of CD8 coreceptor function revealed by crystallographic analysis of a murine CD8alphaalpha ectodomain fragment in complex with H-2Kb. Immunity. 1998 Oct;9(4):519-30. PMID:9806638

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Eric Martz