Sandbox2 Eric Martz
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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
The first 136* sequences found in Swiss-Prot by a single iteration of PSI-BLAST are for MHC class I molecules from diverse species. After that come non-MHC class I, namely multiple sequences each of Hereditary hemochromatosis protein, Zinc-alpha-2-glycoprotein, IgG receptor FcRn large subunit, and MHC class II (which does not bind to CD8).
| 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 | 136* | 8 98466 98587 | 7.8 | 0.33 | 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
- ↑ 1.0 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
- ↑ 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