Three-Dimensional Structure Prediction of the Interaction of CD34 with the SH3 Domain of Crk-L

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Abstract
The monomeric 115-kDa surface protein CD34, which is present on many stem cell populations, has been useful to enumerate the quality and viability of cell suspensions for engraftment. Although these studies assure the validity of CD34 as a stem cell marker, the functional role of this molecule has not been defined. CD34 has been demonstrated to regulate adhesion, differentiation, and proliferation of hematopoietic stem cells and other progenitors. The cytoplasmic domain of CD34 is known to be essential for its function. However, it is not clear how this domain's interactions with other molecules support the functional activity of CD34. Here we show that the cytoplasmic tail of CD34 is structurally similar to the carboxyl terminus of the gap junction protein Connexin 43 (Cx43). Because the activity of CD34 is mediated through its interaction with an SH3 domain of an intracellular protein, we attempted to define the SH3 binding region and amino acids involved in this interaction. We identified Glu325 to Ser334 as potential SH3 binding sites. Our results suggest that the interaction of the cytoplasmic tail of CD34 with the shallow proline-rich motif-binding groove of Crk-L is essential for the function of CD34 in stem cell development.