Lodowski David T, Palczewski Krzysztof
Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106-4965, USA.
Curr Opin HIV AIDS. 2009 Mar;4(2):88-95. doi: 10.1097/COH.0b013e3283223d8d.
Class A G protein-coupled receptors (GPCRs), including the chemokine receptors, CCR5 and CXCR4, share a seven transmembrane-spanning alpha-helix architecture that accommodates signal propagation from across biological membranes. CXCR4 and CCR5 are utilized as co-receptors during HIV viral entry and, therefore, crystal structures of GPCRs aid in the understanding of their function in viral entry.
Recent progress in structure determination of class A GPCRs, which include vertebrate and invertebrate rhodopsin as well as adrenergic and adenosine receptors, provides molecular templates for how this diverse group of transmembrane receptors functions. Each of these GPCRs differs in how specific ligands bind to the transmembrane core, underscoring that additional structures of GPCRs from other subfamilies are needed to facilitate rational drug design. More recent studies also indicate a need to consider the more complex character of GPCRs, such as their oligomerization and dynamics.
Recently, the atomic structures of invertebrate rhodopsin, beta1-adrenergic and beta2-adrenergic receptors and the A(2A)-adenosine receptor have been solved via X-ray crystallography. The impact that these structures have on the biochemistry of viral entry and signal transduction is discussed. Because the chemokine receptors have proven refractory to structural studies thus far, further structural study of the chemokine receptors will be essential to understanding ligand binding, activation and function as co-receptors during viral entry.
A类G蛋白偶联受体（GPCR），包括趋化因子受体CCR5和CXCR4，具有七跨膜α螺旋结构，可实现跨生物膜的信号传导。CXCR4和CCR5在HIV病毒进入过程中用作共受体，因此，GPCR的晶体结构有助于理解其在病毒进入中的功能。
A类GPCR结构测定的最新进展，包括脊椎动物和无脊椎动物视紫红质以及肾上腺素能和腺苷受体，为这类多样的跨膜受体如何发挥功能提供了分子模板。这些GPCR中的每一种在特定配体与跨膜核心结合的方式上都有所不同，这突出表明需要其他亚家族GPCR的更多结构来促进合理的药物设计。最近的研究还表明需要考虑GPCR更复杂的特性，例如它们的寡聚化和动力学。
最近，通过X射线晶体学解析了无脊椎动物视紫红质、β1肾上腺素能受体和β2肾上腺素能受体以及A2A腺苷受体的原子结构。讨论了这些结构对病毒进入和信号转导生物化学的影响。由于到目前为止趋化因子受体已被证明难以进行结构研究，因此对趋化因子受体进行进一步的结构研究对于理解病毒进入过程中作为共受体的配体结合、激活和功能至关重要。
