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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 DGEDQ TQDTE L
H-2Kb PEDK NGEEL IQDME L


2VAA chain A
Server Sequences Q226* APD
ConSurf-DB 144 4 1.72

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