4qam | pdb_00004qam

Crystal Structure of the RPGR RCC1-like domain in complex with the RPGR-interacting domain of RPGRIP1

spinqualitylabelsall models 4qam, resolution 1.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qam is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.83Å Ligands: GOL, MG, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease RPGR_HUMAN Primary ciliary dyskinesia;Achromatopsia;Primary ciliary dyskinesia - retinitis pigmentosa;Cone rod dystrophy;Retinitis pigmentosa. Defects in RPGR are the cause of retinitis pigmentosa type 3 (RP3) [MIM:300029; also known as X-linked retinitis pigmentosa 3 (XLRP-3) or retinitis pigmentosa type 15 (RP15). A X-linked retinal dystrophy belonging to the group of pigmentary retinopathies. RP is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. In RP3, affected males have a severe phenotype, and carrier females show a wide spectrum of clinical features ranging from completely asymptomatic to severe retinitis pigmentosa. Heterozygous women can manifest a form of choroidoretinal degeneration which is distinguished from other types by the absence of visual defects in the presence of a brilliant, scintillating, golden-hued, patchy appearance most striking around the macula, called a tapetal-like retinal reflex. Defects in RPGR are the cause of retinitis pigmentosa and sinorespiratory infections with or without deafness (RPDSI) [MIM:300455. A disease characterized by the association primary ciliary dyskinesia features with retinitis pigmentosa. Some patients also manifest deafness. Defects in RPGR are the cause of cone-rod dystrophy X-linked type 1 (CORDX1) [MIM:304020; also known as cone dystrophy 1 (CO1). CORDs are inherited retinal dystrophies belonging to the group of pigmentary retinopathies. CORDs are characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa. In CORDX1 the degree of rod-photoreceptor involvement can be variable, with degeneration increasing as the disease progresses. Affected individuals (essentially all of whom are males) present with decreased visual acuity, myopia, photophobia, abnormal color vision, full peripheral visual fields, decreased photopic electroretinographic responses, and granularity of the macular retinal pigment epithelium. Although penetrance appears to be nearly 100%, there is variable expressivity with respect to age at onset and severity of symptoms. Defects in RPGR are a cause of macular degeneration X-linked atrophic (MDXLA) [MIM:300834. MDXLA is an ocular disorder characterized by macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. Some patients manifest extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) show normal cone and rod responses in some affected males despite advanced macular degeneration. Function RPGR_HUMAN Could be a guanine-nucleotide releasing factor. Plays a role in ciliogenesis. Probably regulates cilia formation by regulating actin stress filaments and cell contractility. Plays an important role in photoreceptor integrity. May play a critical role in spermatogenesis and in intraflagellar transport processes (By similarity). May be involved in microtubule organization and regulation of transport in primary cilia. Publication Abstract from PubMed RPGR-interacting protein 1 (RPGRIP1) is mutated in the eye disease Leber congenital amaurosis (LCA) and its structural homolog, RPGRIP1-like (RPGRIP1L), is mutated in many different ciliopathies. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR). RPGR is mutated in X-linked retinitis pigmentosa and is located in photoreceptors and primary cilia. We solved the crystal structure of the complex between the RPGR-interacting domain (RID) of RPGRIP1 and RPGR and demonstrate that RPGRIP1L binds to RPGR similarly. RPGRIP1 binding to RPGR affects the interaction with PDEdelta, the cargo shuttling factor for prenylated ciliary proteins. RPGRIP1-RID is a C2 domain with a canonical beta sandwich structure that does not bind Ca(2+) and/or phospholipids and thus constitutes a unique type of protein-protein interaction module. Judging from the large number of C2 domains in most of the ciliary transition zone proteins identified thus far, the structure presented here seems to constitute a cilia-specific module that is present in multiprotein transition zone complexes. C2 domains as protein-protein interaction modules in the ciliary transition zone.,Remans K, Burger M, Vetter IR, Wittinghofer A Cell Rep. 2014 Jul 10;8(1):1-9. doi: 10.1016/j.celrep.2014.05.049. Epub 2014 Jun , 26. PMID:24981858 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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