Lyons Joseph A, Parker Joanne L, Solcan Nicolae, Brinth Alette, Li Dianfan, Shah Syed T A, Caffrey Martin, Newstead Simon
Schools of Medicine and Biochemistry & Immunology, Trinity College Dublin, Dublin, Ireland.
Department of Biochemistry, University of Oxford, Oxford, UK.
EMBO Rep. 2014 Aug;15(8):886-93. doi: 10.15252/embr.201338403. Epub 2014 Jun 10.
An enigma in the field of peptide transport is the structural basis for ligand promiscuity, as exemplified by PepT1, the mammalian plasma membrane peptide transporter. Here, we present crystal structures of di- and tripeptide-bound complexes of a bacterial homologue of PepT1, which reveal at least two mechanisms for peptide recognition that operate within a single, centrally located binding site. The dipeptide was orientated laterally in the binding site, whereas the tripeptide revealed an alternative vertical binding mode. The co-crystal structures combined with functional studies reveal that biochemically distinct peptide-binding sites likely operate within the POT/PTR family of proton-coupled symporters and suggest that transport promiscuity has arisen in part through the ability of the binding site to accommodate peptides in multiple orientations for transport.
肽转运领域的一个谜是配体混杂性的结构基础，哺乳动物质膜肽转运体PepT1就是一个例子。在此，我们展示了PepT1细菌同源物的二肽和三肽结合复合物的晶体结构，这些结构揭示了在单个位于中心的结合位点内运作的至少两种肽识别机制。二肽在结合位点中呈横向取向，而三肽则呈现出另一种垂直结合模式。共晶体结构与功能研究相结合表明，在质子偶联同向转运体的POT/PTR家族中可能存在生化性质不同的肽结合位点，并表明转运混杂性部分是由于结合位点能够以多种取向容纳肽以进行转运而产生的。
